2 research outputs found
ILā4 induces proliferation in prostate cancer PC3 cells under nutrientādepletion stress through the activation of the JNKāpathway and survivin upāregulation
Interleukin (IL)ā4 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 ILā4 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 nutrientādepleted environment, ILā4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrientādepletion stress, ILā4 activates mitogenāactivated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAPāsignalingāspecific inhibitors, it was shown that ILā4āinduced proliferation is mediated by JNK activation. In fact, JNKāinhibitorāV (JNKiāV) stunted ILā4āmediated cell proliferation. Furthermore, it was found that ILā4 induces survivin upāregulation in nutrientādepleted cancer cells. Using survivināshortāhairpināRNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of ILā4āmediated proliferation. In addition, the significance of survivin upāregulation 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 ā4 could induce proliferation in cancer cells from multiple origins: MDAāMBā231 (breast), A253 (head and neck), and SKOVā3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, ILā4 triggers a simultaneous activation of the JNKāpathway and the upāregulation of survivin turning on a cancer proliferation mechanism. J. Cell. Biochem. 113: 1569ā1580, 2012. Ā© 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90542/1/24025_ftp.pd
IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin upregulation
Interleukin (IL)ā4 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 ILā4 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 nutrientādepleted environment, ILā4 induces proliferation in prostate cancer PC3 cells. In these cells, under nutrientādepletion stress, ILā4 activates mitogenāactivated protein kinases (MAPKs), including Erk, p38, and JNK. Using MAPāsignalingāspecific inhibitors, it was shown that ILā4āinduced proliferation is mediated by JNK activation. In fact, JNKāinhibitorāV (JNKiāV) stunted ILā4āmediated cell proliferation. Furthermore, it was found that ILā4 induces survivin upāregulation in nutrientādepleted cancer cells. Using survivināshortāhairpināRNAs (shRNAs), it was demonstrated that in this milieu survivin expression above a threshold limit is critical to the mechanism of ILā4āmediated proliferation. In addition, the significance of survivin upāregulation 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 ā4 could induce proliferation in cancer cells from multiple origins: MDAāMBā231 (breast), A253 (head and neck), and SKOVā3 (ovarian). Overall, these findings suggest that in a tumor microenvironment under stress conditions, ILā4 triggers a simultaneous activation of the JNKāpathway and the upāregulation of survivin turning on a cancer proliferation mechanism. J. Cell. Biochem. 113: 1569ā1580, 2012. Ā© 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90542/1/24025_ftp.pd