10 0 0 10 60 379 Tm Proc. MCF-7 cells were labeled with luciferase expression vector. Our data showed that ectopic expression of AKR1B10 in breast cancer cells . Clark, J.D., Lim, L.L., Kriz, R.W., Ramesha, C.S., Sultzman, L.A., Lin, A.Y., Milona, L. and Knopf, J. L. Cell 65:10431051, 1991. /T1_2 1 Tf endobj The site is secure. (Signaling Networks: Information Flow,)Tj The rate of phosphorylation of cell-associated diC/sub 10/ was decreased 50% by PDGF treatment. Figure 1.. AKR1B10 promotes lipogenesis of cancer. 0 1 TD These results suggest that the inability of AII to maintain tension, unlike PE, is due to its inability to produce DAG continuously and activate protein kinase C. Insulin, concanavalin A, EGF, IFG-I and vanadate activate de novo phosphatidic acid and diacylglycerol synthesis, C-kinase, and glucose transport in BC3H-1 myocytes, Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267, Substrate selectivity of diacylglycerol kinase in PDGF-stimulated 3T3 cells, Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats, Evidence for a requirement of agonist-induced diacylglycerol production during tonic contraction of rat aorta. /T1_0 1 Tf ET /T1_1 1 Tf (Alexandra C. Newton, Martin D. Bootman and John)Tj ET AKR1B10 is not expressed in normal breast, but up-regulated in breast cancer, indicating a poor prognosis. In breast cancer cells, the activated ERK signaling by AKR1B10 enhanced cell growth and proliferation through phosphorylation activation of p90RSK and MSK and expression of cyclin D1, and this was proven by pharmacological inhibition of ERK1/2 activity using MEK1/2 inhibitors U0126 and PD98059. and Hendrickson, W.A. 4B). (For additional articles in this collection, see )Tj *, p<0.05 and **, p<0.01 when compared to vector control. <>stream In the breast cancer cells, AKR1B10 promotes lipogenesis and increases cellular lipid second messengers PIP2, IP3 and DAG, which activates the PKC/ERK signaling cascade. Nature 349:426428, 1991. Chem. PubMed BT In summary, this study obtained a series of data that mechanistically address the oncogenic role of AKR1B10 in growth and progression of breast cancer. These compounds were tested in human platelets. (B) Raf/MER/ERK activation by AKR1B10, showing p-Raf, p-MEK and p-ERK1/2 levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. ET DAG second messengers: molecular switches and growth control Adv Exp Med Biol. . (Jeremy Thorner, Tony Hunter, Lewis C. Cantley, et)Tj Plating efficiency was calculated as: Colony number/seeded cell number. <> The development of specific inhibitors of DAG kinase and DAG lipase, in conjunction with mass quantification of DAG levels as used here, will providemore further insights into the regulation of DAG second messengers.less, The authors have reported that insulin stimulates de novo synthesis of phosphatidic acid (PA) which is metabolized directly to diacylglycerol (DG) in BS3H-1 myocytes; this is accompanied by increases in C-kinase activity in membrane and cytosolic extracts. J. Biol. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. (B) Levels of various subspecies of DAG in MCF-7 (upper), BT-20 (lower left) and HCT-8 (lower right) cells. Would you like email updates of new search results? FOIA /T1_2 1 Tf 10 0 0 10 60 335 Tm CAS AKR1B10 increases fatty acid synthesis by stabilizing ACCA, enhancing cellular phospholipids and sterols. 0 1.00001 TD Figure 6.. AKR1B10 promotes tumor growth in female nude mice. BT Google Scholar. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips. 550201* - Biochemistry- Tracer Techniques, - Fed. official website and that any information you provide is encrypted Tumor volume was monitored by both in vivo imaging and caliper measurements. PMC Lipids are a group of water-insoluble intracellular molecules, such as phosphoglycerides, triglycerides, sphingolipids and sterols. ( Superfamily)Tj Mice were placed onto a warm stage inside a light-tight camera box with continuous exposure to isoflurane. Chem. 2021 Aug 21;11(1):163. doi: 10.1186/s13578-021-00677-3. As shown in Fig. In many cases the response of the cell membrane is the production of small rapidly diffusible "second messenger" substances inside the cell. )Tj (Protein Regulation in Signal Transduction)Tj Acad. (\240)Tj A: We can say that Hormones can be described as the chemical secreted by specialized cells of endocrine. ET ET Thus we further observed the effect of AKR1B10 on proliferation and tumorigenesis of breast cancer cells. Conflict of interest: Authors declare no conflict of interest with the contents of this article. Disclaimer, National Library of Medicine *, p<0.05 and **, p<0.01 when compared to vector control. Science 238:17261728, 1987. 6, MCF-7 tumors with AKR1B10 expression grew faster than vector control tumors. (A) Mechanisms responsible for producing and removing second . In contrast, phosphorylation of these PKC isoforms decreased in BT-20 cells with AKR1B10 silencing by two different siRNAs that target different regions of mRNA. (B) Plating efficiency of MCF-7 cells in cell culture dishes. We further assessed the effect of AKR1B10 on clonogenic growth of MCF-7 cells in three-dimensional (3D) culture in growth factor-reduced extracellular matrix that mimics in vivo environment of mammary epithelial cells. 244 0 obj endobj T* (Doreen Cantrell)Tj 265:14, 1990. 468 0 0 60 72 126 cm ET total glycerolipids, although none were as effective as insulin, which increased (/sup 3/H)DG 400% in 1 minute. DAG and IP 3 are second messengers that can act independently or in unison. Therefore, AKR1B10-induced lipogenesis may have critical impact in cancer development and progression. This fusion protein translocated to phospholipid vesicles in an phosphatidylserine (PS)-dependent manner. The selectivity of DAG kinase may play a key role in the formation of arachidonoyl species of PI. official website and that any information you provide is encrypted Feig, L.A. and Cooper, G.M. Together these data suggest that AKR1B10 promotes clonogenic growth and proliferation of breast cancer cells. 4A, ectopic expression of AKR1B10 in MCF-7 increased the cell growth and proliferation compared to the empty vector control, whereas silencing of AKR1B10 in BT-20 cells decreased the cell proliferation. BT Analytical data of DAG subspecies demonstrated that targeted expression of AKR1B10 markedly increased the levels of majority of 16 DAG subspecies, but AKR1B10 silencing led to decrease of DAG subspecies (Fig. BT DAG activates important oncogenic signaling molecule PKC, and IP3 provokes ER-mediated calcium signaling, further activating PKC. This pathway may be involved in stimulating glucose transport and other metabolic processes. 10 0 0 10 308 321 Tm In: Honn, K.V., Nigam, S., Marnett, L.J. 8:32353243, 1988. 10 0 0 10 318 461 Tm 8 0 0 8 260.42407 754 Tm Keywords: The 4C). CAS J. Biol. The term second messenger was coined upon the discovery of these substances in order to distinguish them from hormones and other molecules that function outside the cell as "first messengers" in the transmission of biological information. Acini were photographed by a phase contrast microscopy (Carl Zeiss, CA). 1B). 1994 Sep;267(3 Pt 1):C659-78. The organic phase was collected and dried by speed vacuum. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. Second Messengers Often the extracellular message is a chemical (hormone or neurotransmitter), which binds to its receptor on the cell membrane, which in turn triggers events in the membrane. 10 0 0 10 50 471 Tm ET The minimal sequence required for PDBu binding was elucidated by deletion analysis. Advances in Experimental Medicine and Biology, vol 400. BT Metabotropic signaling with G-protein coupling. The .gov means its official. (Michael J. Lee and Michael B. Yaffe)Tj Scram, scrambled siRNA; SiR-1, AKR1B10 siRNA-1; and SiR-2, AKR1B10 siRNA-2. 148 0 obj ET (Downloaded from )Tj Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG) and inositol triphosphate (IP3). At indicated time points, cells were trypsinized, stained with trypan blue and counted by a Vi-cell counter (Beckman coulter, CA). Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. 10 0 0 10 308 495 Tm Exp. Phospholipids are essential components of bio-membranes and important second messengers in cellular signaling transduction, regulating various pathophysiological processes [1-3]. BT Search terms: Advanced search options. Diacylglycerol(DAG) derived from phosphatidylinositol activates protein kinase C in agonist-stimulated cells. They greatly amplify the strength of the signal, cause some kind of change in the activity of the cell. BT Download preview PDF. /Im0 Do AKR1B10 expression and lipid synthesis in the MCF-7 (A), BT-20 (B) and HCT-8 (C) cells. Viable cells correlate with the magnitude of Alamar blue reduction (%) following the manufactures instructions. Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. https://doi.org/10.1007/978-1-4615-5325-0_42, Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2, Advances in Experimental Medicine and Biology, Shipping restrictions may apply, check to see if you are impacted, Tax calculation will be finalised during checkout. P30 CA076292/CA/NCI NIH HHS/United States, P30 DK020579/DK/NIDDK NIH HHS/United States, NCI CPTC Antibody Characterization Program. Figure 1.. AKR1B10 promotes lipogenesis of cancer cells. (C) Caliper measurements of the tumor size. Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA, Andrew F.G. Quest,Sujoy Ghosh,Wen Qin Xie&Robert M. Bell, You can also search for this author in Tumor volume was measured using in vivo bioluminescent imaging with an IVIS VR imaging system (Xenogen, CA) and also measured by Vernier caliper. In these cells, phospho-p90RSK, phospho-MSK and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cascade with MEK1/2 inhibitors U0126 and PD98059 eradicated induction of phospho-p90RSK, phospho-MSK and Cyclin D1. 194 0 obj Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. The pathway begins with the binding of extracellular primary messengers such as epinephrine, acetylcholine, and hormones AGT, GnRH, GHRH, oxytocin, and TRH, to their respective receptors. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. Conflict of interest: Authors declare no conflict of interest with the contents of this article. These data suggest that the ERK1/2 signaling activated by AKR1B10 promotes cell growth and proliferation through the targets p90RSK, MSK and cyclin D1 in the breast cancer cells. IP3 diffuses freely into cytoplasm, triggering endoplasmic reticulum (ER)-mediated Ca2+ signaling; DAG remains in cell membrane and activates protein kinase C (PKC) [5-7]. (1994) J. Biol. DAG activates protein kinase C and IP3 binds to a receptor on the endoplasmic reticulum to release calcium from intracellular stores. IS, internal standard. 1997;400A:297-303. doi: 10.1007/978-1-4615-5325-0_42. Lipids were dissolved in 50 l of chloroform/methanol (2:1, v/v). endstream IS, internal standard. /T1_2 1 Tf Second Messengers Cells were prelabeled with /sup 32/P and treated with PDGF or carrier. The results showed that MCF-7 cells with AKR1B10 expression formed more and larger acini than vector control cells (Fig. doi: 10.1152/ajpcell.1994.267.3.C659. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced (/sup 32/P)phosphatidic acid formation in SHR. Fatty acids are essential components of various lipids, such as triglycerides and phosphoglycerides. In fact, AKR1B10 is upregulated in multiple solid cancers, such as liver, breast, lung and pancreatic cancers, being a potential prognostic biomarker [29-32]. Protein kinase C isozymes are stereospecifically regulated by diacylglycerol (DAG) second messengers or phorbol esters (PDBu) through interactions with cysteine-rich PKC segments (Cysl, Cys2) containing six conserved cysteines (C) and two conserved histidines (H) in the pattern H-X12-C-X1014-C-X2-C-X4-H-X2-C-X7-C where X are non-conserved residues. These data suggest that AKR1B10 participates in regulation of lipid second messengers in breast cancer cells. (1997). *, p<0.05 and **, p<0.01 when compared to vector control. The DAG formed was in a pool where it did not activate protein kinase C. Thrombin-stimulation of MOG-treated platelets resulted in DAG levels 10-fold higher than control platelets. ET The second messenger pathway which concerns the intracellular action of Ca2+ ions is involved in a variety of actions that include the collaboration with DAG for the activation of PKC and the calcium-modulated protein (calmodulin or Cam) kinase pathway. 50 545 m Cell. Ahmed, S., Kozma, R., Lee, J., Monfries, C., Harden, N. and Louis, L. Biochem. 0 1 TD endstream Relative quantification data generated in same batches are appropriate to compare the change of an analyte in AKR1B10 expression or AKR1B10 silencing samples to the corresponding control. DAG and subspecies were measured quantitatively by liquid chromatography-mass spectrum as described in Methods and Materials. Similar to other. Total lipids were extracted as described [15,38]. ET (Douglas R. Green and Fabien Llambi)Tj The high proliferation of cancer cells depends on lipid synthesis to meet both the needs of biomembrane synthesis in cell division and function as signal molecules, stimulating cell growth and proliferation [5]. (al. Such raf-1 translocation to the membrane brings it in proximity to activated GTP-ras which interacts directly with raf-1 during signal transduction. /T1_0 1 Tf This study showed that AKR1B10 promoted lipogenesis and activated DAG-mediated PKC/ERK signaling cascade. Their findings raise the possibility that activation of receptors having associated tyrosine kinase activity may provoke some cellular responses through de novo PA/GD synthesis and C-kinase activation. Growth rate of cells was measured using Alamar blue (ABD Serotec, UK) reduction assay. to target molecules in the cytosol and/or nucleus. (A) PKC activation by AKR1B10, showing p-PKC (Thr505), p-PKC (Ser744/748) and p-PKC/II (Thr638/641) levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. 10 0 0 10 60 437 Tm USA 83:11841188, 1986. government site. Epub 2006 May 6. Each nude mouse was implanted with a 1.7 mg of 17-estradiol pellet (Innovative Research of America, CA) to support MCF-7 proliferation. (Alexandra C. Newton, Martin D. Bootman and John D. Scott)Tj Correlation analyses were conducted using Spearman correlation and multivariate canonical correlation. Zeman RJ, Wen X, Ouyang N, Brown AM, Etlinger JD. IP 3, DAG, and Ca 2+ are second messengers in the phosphoinositol pathway. Quest, A.F.G., Bioomenthal, J.B., Bardes, E.S.G. PubMedGoogle Scholar, Wayne State University, Detroit, Michigan, USA, Vanderbilt University, Nashville, Tennessee, USA, 1997 Springer Science+Business Media New York, Quest, A.F., Ghosh, S., Xie, W.Q., Bell, R.M. . Oppositely, silencing of AKR1B10 in BT-20 cells led to decrease in total lipids, PIP2 and IP3 (Fig. 189 0 obj J. Biol. Ctrl: control. The beta isozymes of PLC are regulated by G-proteins (G-alphaq/11 and G-betagamma) Berridge (1989), Gilman (1989). Imaging times were controlled equally at 15 sec, and signal quantification was performed by an acquisition and analysis software (Living ImageVR, Xenogen, CA) and expressed as amount of Flux (photons per second). 3C). It was also discovered that cyclooxygenase products were responsible for further stimulation (a positive feed-back) of phospholipase C activity, while diacylglycerol provided a negative feed-back control over receptor-stimulated phospholipase C activity and inhibited ADP release. AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study. In brief, lipids were extracted from 510 6 cells using a modified Bligh-Dyer method in the presence of an internal standard DG15:0-15:0 (0.5 g per sample). (Vertebrate Reproduction)Tj Signal transduction in vascular smooth muscle: diacylglycerol second messengers and PKC action. Although repetitive observations were not conducted in these breast cancer cells with targeted expression or silencing of AKR1B10, we believe that the carbonyl detoxification mechanism of AKR1B10 may also contribute to the cell growth and proliferation. (Second Messengers)Tj Under these conditions the DAG signal was somewhat long-lived but was still metabolized, presumably by the lipase pathway. (Signaling Pathways that Regulate Cell Division)Tj <>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Type/Page>> In contrast, early thrombin-induced phosphoinositide metabolism, when, A possible role for protein kinase C during the tonic phase of arterial contraction was examined in rat aorta by observing the effects of the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA), on angiotensin II (AII)-induced responses. **, p<0.01 when compared to AKR1B10 Control cells. (G\366khan S. Hotamisligil and Roger J. Davis)Tj Tel: (314) 747-0677. IP3: (n-s-tl), IP3 An intracellular second messenger molecule that stimulates the endoplasmic reticulum of the cell to release calcium. Second Messengers Bioenergetics Investigating Photosynthesis Biological Molecules ATP Carbohydrates Condensation Reaction DNA and RNA DNA replication Denaturation Enzymes Factors Affecting Enzyme Activity Fatty Acids Hydrolysis Reaction Inorganic Ions Lipids Measuring enzyme-controlled reactions Monomers Monomers and Polymers Monosaccharides uuid:b03733e8-1dd1-11b2-0a00-aa00a8a7ebff Part of Springer Nature. Nature 320:540543, 1986. (Copyright \251 2016 Cold Spring Harbor Laboratory Press; all rights rese\ rved)Tj 2017 May 16;8(20):33694-33703. doi: 10.18632/oncotarget.16624. 280:233241, 1991. These data suggest that AKR1B10 promotes breast cancer growth in vivo by activating the PKC/ERK signaling pathway, being an oncogenic protein in breast cancer growth and progression. This result was confirmed in HCT-8 cells derived from colon cancer (Fig. BT Herein we found that AKR1B10 activates the cellular lipid second messengers and thus triggers the lipid-mediated cell proliferative signal transduction. We used the LC-Mass Core facility of Washington University at St Louis to quantitatively measure total DAG and 16 subspecies in cells with targeted expression or silencing of AKR1B10 (Supplemental Figure S1). 122 0 obj This site needs JavaScript to work properly. and transmitted securely. and Bell, R.M. It is noteworthy to note that AKR1B10 can promote cell survival through protection from reactive carbonyl lesions [13,17,37]. 5B). 2Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. BT PMC legacy view Cell suspensions (50 ml/inoculation) were subcutaneously injected with a 25-gauge needle into mammary fat pads of female nude mice at 5 weeks old. 2015 Jun 5;234:274-81. doi: 10.1016/j.cbi.2014.11.013. Diaz-Laviada, I., Larrodera, P., Diaz-Meco, M.T., Cornet, M.E., Guddal, P.H., Johansen, T. and Moscat, J. EMBO J. On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents. Clipboard, Search History, and several other advanced features are temporarily unavailable. Phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) are two major mediators of cellular lipid messengers. BT BT AKR1B10 knockdown was examined using Western blot. 2022 Springer Nature Switzerland AG. Left panel: Quantitative analysis of band intensity. ET Activation of protein kinase C with TPA prior to and during AII exposure converted the normally transient contraction to a more sustained, tonic pattern. 10 0 0 10 242.84967 212 Tm The results showed that AKR1B10 expression and resulting activation of the MEK/ERK signaling increased the phosphorylation of p90RSK and MSK and cyclin D1 expression; and the MEK1/2 inhibitor U0126 abolished the p90RSK and MSK phosphorylation and cyclin D1 expression stimulated by AKR1B10 (Fig. Two analogs were potent inhibitors in vitro, 1-monooleoylglycerol(MOG,K/sub I/ = 91 ..mu..M) and diotanoylethyleneglycol (diC/sub 8/EG, K/sub I/ = 58 ..mu..M). 4A The beta isozymes of PLC are regulated by G-proteins (G-alphaq/11 and G-betagamma) Berridge (1989), Gilman (1989). ( )Tj 10/ and PI/sub 10/ was consistently decreased. In breast cancer, AKR1B10 is upregulated in ductal carcinoma in situ (DCIS) and invasive, metastatic and recurrent tumors and correlates with tumor size, lymph node metastasis, and disease-related death. ET Increased incorporation into phospholipids and triacylglycerols and to a lesser extent monoacylglycerol was also noted. 10 0 0 10 50 529 Tm PIP2 second messenger system is the most important lipid second messengers that mediate cell signaling transduction. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas, Clinical cancer research : an official journal of the American Association for Cancer Research, AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker, Epidermal growth factor induces tumour marker AKR1B10 expression through activator protein-1 signalling in hepatocellular carcinoma cells, AKR1B10 promotes breast cancer metastasis through integrin alpha5/delta-catenin mediated FAK/Src/Rac1 signaling pathway. 11 0 0 11 205.27596 579.99988 Tm Ganong, B.R., Loomis, C.R., Hannun, Y.A. 562 545 l However, little is known of the molecular mechanisms of action. The mechanism of enhanced phosphorylation of DAG was studied with dicaprylin (diC/sub 10/) as a probe. Google Scholar. (C) ERK inhibition by a broad PKC inhibitor, Go6893 (10M), showing decreased p-ERK1/2 level by Go6893 in the MCF-7 cells with AKR1B10 expression. Y axis is in log10. A: Joints can be outlined as the point where two parts of the skeletal system are associated with each . However, little is known of the molecular mechanisms of action. Statistical analyses were performed using Student`s t tests or ANOVA with INSTAT statistical analysis package (Graph Pad software, CA). PIP2 is a precursor of the important lipid second messenger diacylglycerol (DAG). /T1_2 1 Tf Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. (http://cshperspectives.cshlp.org/cgi/collection/ )Tj It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. Figure 4.. AKR1B10 promotes growth and proliferation of breast cancer cells. 245 0 obj /T1_1 1 Tf (C) Acinar formation and growth of MCF-7 cells in the Matrigel-based 3D culture. AKR1B10 expression and lipid synthesis in the, Figure 2.. AKR1B10 increases DAG levels in. Figure 4.. AKR1B10 promotes growth and proliferation. Please enable it to take advantage of the complete set of features! BT Federal government websites often end in .gov or .mil. AKR1B10 promotes breast cancer metastasis through integrin 5/-catenin mediated FAK/Src/Rac1 signaling pathway. 2016 Jul 12;7(28):43779-43791. doi: 10.18632/oncotarget.9672. Data processing was conducted with X calibur (Thermo). As shown in Fig. Increased PIP2 and IP3 levels in breast cancer cells encouraged an extended study on DAG and the DAG-mediated signaling transduction. **, p<0.01 when compared to the vector control or PD98059/U0126-treated cells. /T1_2 1 Tf The activated PKCs phosphorylates and activates c-Raf, which in turn phosphorylates and activates MEK, provoking the ERK1/2 signaling [8]. 2A). The p90RSK, MSK and cyclin D1 functions as downstream targets of the ERK1/2 in this process. The new PMC design is here! BT ( on December 11, 2022 - Published by Cold Spring Harbor Laboratory Press\ )Tj Chem. Chem. AKR1B10 promotes biosynthesis of long chain fatty acids by stabilizing ACCA [26]. Natl. 249 0 obj Chem. Accessibility Acad. Dag Second Messengers: Molecular Switches and Growth Control. Bethesda, MD 20894, Web Policies Luciferase-labelled MCF-7 cells with targeted AKR1B10 expression or a vector control were injected subcutaneously into the mammary fat pads of female nude mice (n=5 per group). Q <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> /T1_1 1 Tf 266:32153221, 1991. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR. CrossRef ET 2016-07-20T11:04:33+05:30 3B, phosphorylated c-Raf, MEK1/2 and ERK1/2 all increased in MCF-7 cells with ectopic expression of AKR1B10, but decreased in BT-20 cells with AKR1B10 knockdown. cAMP, cGMP, IP3, DAG. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2. /T1_0 1 Tf eCollection 2021. AKR1B10 is upregulated in human breast cancer and correlates with tumor size and lymph node metastasis [31], but the underlying molecular mechanisms are unclear. ET ET 9:39073912, 1990. 1Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. (B) ERK targeted genes in MCF-7 cell. ET Acetate incorporation into lipid species, including phosphatidylinositol-4,5-bisphosphate (PIP2), inositol-1,4,5- trisphosphate (IP3) and diacylglycerol (DAG), was analyzed by thin layer chromatography (TLC). 2 0 obj Neurosci. Mol Carcinog. Lipid fractions were re-suspended into 50% methanol solution, and radioactivity were measured by scintillation counter (Beckman Instruments). (D) PKC/ERK signaling activity in tumors. ET In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. Briefly, MCF-7 cells (3,000 cells/well) were plated in 96-well plates. Protein lysates, SDS-PAGE and Western blotting were performed as previously described [26]. /T1_1 1 Tf BT https://doi.org/10.1007/978-1-4615-5325-0_42, DOI: https://doi.org/10.1007/978-1-4615-5325-0_42. An official website of the United States government. Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics. As shown in Fig. and Bell, R.M. BT )Tj The p-ERK1/2, p-p90RSK and p-MSK levels and Cyclin D1 expression were increased by AKR1B10 in the cells, and the increased p-p90RSK, p-MSK and Cyclin D1 levels were eradicated by MEK inhibitor, U0126 (10 M). /T1_0 1 Tf The DAG pathway is a message generating pathway that is involved in the activation of enzymes and in turn produces various biological events, including transcription of DNA. At indicated time points, reduced Alamar blue was detected at 590 nm with a fluorescent spectrum (Thermo, CA). /T1_1 1 Tf 10 0 0 10 318 485 Tm /T1_2 1 Tf Western blot results showed that exposure of MCF-7 cells to Go6983 (10 M) abolished phosphorylation activation of ERK1/2 induced by AKR1B10 (Fig. The results showed that ectopic expression of AKR1B10 promoted clonogenic growth in both 2D and 3D cultures and tumorigenesis in nude mice, but silencing of AKR1B10 suppressed growth and proliferation of breast cancer cells. /T1_0 1 Tf Sci. 266:1833018338, 1991. As shown in Fig. Bethesda, MD 20894, Web Policies In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. Cells were trypsinized and suspended in mix of medium and equal volume of Matrigel (BD Bioscience, CA) at 5106/50 ml. These messengers differ in the mechanism by which they are produced and removed, as well as their downstream targets and effects (Figure 8.7A). ET 10 0 0 10 238.36987 554 Tm (In Press), Quest, A.F.G. Only the lipid species with CV < 15% in QC sample were reported. Epub 2014 Nov 22. Figure 7.. Hypothetic model of cell growth. -8.83699 0 Td 5. DiC/sub 8/EG inhibited (70 - 100%) (/sup 32/P/sub i/) incorporation into PA in thrombin-stimulated platelets. 10 0 0 10 308 412.99997 Tm The site is secure. 2018 Oct; 57(10): 13001310. 562 568 l Long chain fatty acids are precursors of lipids and are the main components of biomembrane phospholipids. Zu X, Yan R, Robbins S, Krishack PA, Liao DF, Cao D. Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression, Toxicological sciences : an official journal of the Society of Toxicology, Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer, Oxidative medicine and cellular longevity, Development of a 32P-postlabelling method for the detection of 1,N2-propanodeoxyguanosine adducts of crotonaldehyde in vivo, Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency, International journal of cancer Journal international du cancer, Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10, Proceedings of the National Academy of Sciences of the United States of America, Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels, AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group. 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