Kidney Cancer
Return to Library
|
Free Kidney Cancer Articles |
|
|
|
|
Study findings from Virginia Commonwealth University provide new insights into kidney cancer
2009 JUL 20 - (NewsRx.com) -- "Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on clarifying the mechanism(s) by which glutathione S-transferase (GST)-MDA-7 altered cell survival of human renal carcinoma cells in vitro," scientists in the United States report. "GST-MDA-7 caused plasma membrane clustering of CD95 and the association of CD95 with procaspase-8. GST-MDA-7 lethality was suppressed by inhibition of caspase-8 or by overexpression of short-form cellular FLICE inhibitory protein, but only weakly by inhibition of cathepsin proteases. GST-MDA-7-induced CD95 clustering (and apoptosis) was blocked by knockdown of acidic sphingomyelinase or, to a greater extent, ceramide synthase-6 expression. GST-MDA-7 killing was, in parallel, dependent on inactivation of extracellular signal-regulated kinase 1/2 and on CD95-induced p38 mitogen-activated protein kinase and c-jun NH2-terminal kinase-1/2 signaling. Knockdown of CD95 expression abolished GST-MDA-7-induced phosphorylation of protein kinase R-like endoplasmic reticulum kinase. GST-MDA-7 lethality was suppressed by knockout or expression of a dominant negative protein kinase R-like endoplasmic reticulum kinase that correlated with reduced c-jun NH2-terminal kinase-1/2 and p38 mitogen-activated protein kinase signaling and maintained extracellular signal-regulated kinase-1/2 phosphorylation. GST-MDA-7 caused vacuolization of LC3 through a mechanism that was largely CD95 dependent and whose formation was suppressed by knockdown of ATG5 expression. Knockdown of ATG5 suppressed GST-MDA-7 toxicity. Our data show that in kidney cancer cells GST-MDA-7 induces ceramide-dependent activation of CD95, which is causal in promoting an endoplasmic reticulum stress response that activates multiple proapoptotic pathways to decrease survival," wrote M.A. Park and colleagues, Virginia Commonwealth University. The researchers concluded: "[Mol Cancer Ther 2009;8(5):1280-91]." Park and colleagues published their study in Molecular Cancer Therapeutics (MDA-7/IL-24-induced cell killing in malignant renal carcinoma cells occurs by a ceramide/CD95/PERK-dependent mechanism. Molecular Cancer Therapeutics, 2009;8(5):1280-1291). For additional information, contact P. Dental, Virginia Commonwealth University, Dept. of Biochemistry & Molecular Biology, Massey Cancer Center, School Medical, 401 College St., Box 980035, Richmond, VA 23298, USA. The publisher's contact information for the journal Molecular Cancer Therapeutics is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA. Keywords: United States, Box, Kidney Cancer, Apoptosis, Caspase, Dietary Supplement, Enzyme Research, Enzymology, Glutathione, Kidney, Kinase, Micronutrient, Nephrology, Oncology, Protease, Renal Cancer, Renal Carcinoma, Synthase, Therapy, Transferase, Treatment, Virginia Commonwealth University. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.
|
