Interleukin-17 receptor-like gene is a novel antiapoptotic gene highly expressed in androgen-independent prostate cancer.
We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate cancer cell lines (PC3, DU145, cds1, cds2, and cds3) and tumors compared with the androgen-dependent cell lines (LNCaP and MLC-SV40) and tumors. In an in vivo model of human prostate tumor growth in nude mice (CWR22 xenograft model), IL-17RL expression in tumors was induced by androgen deprivation. The relapsed androgen-independent tumors expressed higher levels of IL-17RL compared with the androgen-dependent tumors. Overexpression of IL-17RL in tumor necrosis factor alpha (TNFalpha)-sensitive LNCaP cells inhibited TNFalpha-induced apoptosis by blocking activation of caspase-3 downstream to caspase-2 and caspase-8. Reciprocally, knocking down IL-17RL expression by small interfering RNA induced apoptosis in all the prostate cancer cell lines studied. Taken together, these results show that IL-17RL is a novel antiapoptotic gene, which may confer partially the property of androgen-independent growth of prostate cancer by promoting cell survival. Thus, IL-17RL is a potential therapeutic target in the treatment of prostate cancer.
You
Zongbing
Z
Center for Tissue Regeneration and Repair, Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Sacramento, California 95817, USA. zyou@ucdavis.edu
Shi
Xu-Bao
XB
DuRaine
Grayson
G
Haudenschild
Dominik
D
Tepper
Clifford G
CG
Lo
Su Hao
SH
Gandour-Edwards
Regina
R
de Vere White
Ralph W
RW
Reddi
A Hari
AH
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D061945:Caspase Inhibitors; C448419:IL17RC protein, human; D007527:Isoenzymes; D034741:RNA, Small Interfering; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases