Overexpression of Cdc25B, an androgen receptor coactivator, in prostate cancer.
Cdc25B is a dual-specific phosphatase that mediates cell cycle progression by activating the cyclin-dependent kinases. It has been shown to possess oncogenic potential. To elucidate its potential contribution to human prostate cancer development, the expression profile of Cdc25B protein in human patients was analysed by immunohistocytochemistry. Cdc25B is frequently overexpressed in human prostate cancer tissues (29 of 30; 97%). In addition, the overexpression is more profound in the tumors of high combined Gleason scores and in late stages. Subsequently, we demonstrated that Cdc25B acts as a coactivator for AR in a hormone-dependent manner in the prostate cancer cell line, LNCaP. This coactivator function, surprisingly, is independent of its cell cycle functions. Cdc25B, on the other hand, directly interacts with AR as evidenced in GST-pull down and mammalian two-hybrid assays. In addition, it is also able to enhance AR-mediated transcription in synergy with other coactivators, including CREB-binding protein (CBP) and p300/CBP associated factor. Therefore, upregulation of Cdc25B in human prostate cancer and its interplay with AR may contribute to prostate cancer development.
Ngan
Elly S W
ES
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Hashimoto
Yoshihiro
Y
Ma
Zhi-Qing
ZQ
Tsai
Ming-Jer
MJ
Tsai
Sophia Y
SY
D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D011944:Receptors, Androgen; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases