IL‐4 induces proliferation in prostate cancer PC3 cells under nutrient‐depletion stress through the activation of the JNK‐pathway and survivin up‐regulation
dc.contributor.author | Roca, Hernan | en_US |
dc.contributor.author | Craig, Matthew J. | en_US |
dc.contributor.author | Ying, Chi | en_US |
dc.contributor.author | Varsos, Zachary S. | en_US |
dc.contributor.author | Czarnieski, Paul | en_US |
dc.contributor.author | Alva, Ajjai S. | en_US |
dc.contributor.author | Hernandez, James | en_US |
dc.contributor.author | Fuller, David | en_US |
dc.contributor.author | Daignault, Stephanie D. | en_US |
dc.contributor.author | Healy, Patrick N. | en_US |
dc.contributor.author | Pienta, Kenneth J. | en_US |
dc.date.accessioned | 2012-04-04T18:42:43Z | |
dc.date.available | 2013-06-11T19:15:42Z | en_US |
dc.date.issued | 2012-05 | en_US |
dc.identifier.citation | Roca, Hernan; Craig, Matthew J.; Ying, Chi; Varsos, Zachary S.; Czarnieski, Paul; Alva, Ajjai S.; Hernandez, James; Fuller, David; Daignault, Stephanie; Healy, Patrick N.; Pienta, Kenneth J. (2012). "IL‐4 induces proliferation in prostate cancer PC3 cells under nutrient‐depletion stress through the activation of the JNK‐pathway and survivin up‐regulation ." Journal of Cellular Biochemistry 113(5): 1569-1580. <http://hdl.handle.net/2027.42/90542> | en_US |
dc.identifier.issn | 0730-2312 | en_US |
dc.identifier.issn | 1097-4644 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/90542 | |
dc.description.abstract | Interleukin (IL)‐4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumor microenvironment of cancer patients where it correlates with the grade of malignancy. The direct effect of IL‐4 on cancer cells has been associated with increased cell survival; however, its role in cancer cell proliferation and related mechanisms is still unclear. Here it was shown that in a nutrient‐depleted environment, IL‐4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrient‐depletion stress, IL‐4 activates mitogen‐activated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAP‐signaling‐specific inhibitors, it was shown that IL‐4‐induced proliferation is mediated by JNK activation. In fact, JNK‐inhibitor‐V (JNKi‐V) stunted IL‐4‐mediated cell proliferation. Furthermore, it was found that IL‐4 induces survivin up‐regulation in nutrient‐depleted cancer cells. Using survivin‐short‐hairpin‐RNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of IL‐4‐mediated proliferation. In addition, the significance of survivin up‐regulation in a stressed environment was assessed in prostate cancer mouse xenografts. It was found that survivin knockdown decreases tumor progression in correlation with cancer cell proliferation. Furthermore, under nutrient depletion stress, IL ‐4 could induce proliferation in cancer cells from multiple origins: MDA‐MB‐231 (breast), A253 (head and neck), and SKOV‐3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, IL‐4 triggers a simultaneous activation of the JNK‐pathway and the up‐regulation of survivin turning on a cancer proliferation mechanism. J. Cell. Biochem. 113: 1569–1580, 2012. © 2011 Wiley Periodicals, Inc. | en_US |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | JNK | en_US |
dc.subject.other | IL‐4 | en_US |
dc.subject.other | PROLIFERATION | en_US |
dc.subject.other | NUTRIENT‐DEPLETION STRESS | en_US |
dc.subject.other | PROSTATE CANCER | en_US |
dc.subject.other | SURVIVIN | en_US |
dc.title | IL‐4 induces proliferation in prostate cancer PC3 cells under nutrient‐depletion stress through the activation of the JNK‐pathway and survivin up‐regulation | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Genetics | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.contributor.affiliationum | Department of Urology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.contributor.affiliationum | Department of Urology, Comprehensive Cancer Center, University of Michigan, 1500 E Medical Center Dr, 7431 CCC, Ann Arbor, MI 48109. | en_US |
dc.contributor.affiliationum | Division of Biostatistics, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109 | en_US |
dc.identifier.pmid | 22174091 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/90542/1/24025_ftp.pdf | |
dc.identifier.doi | 10.1002/jcb.24025 | en_US |
dc.identifier.source | Journal of Cellular Biochemistry | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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