Antagonism between PTEN/MMAC1/TEP-1 and androgen receptor in growth and apoptosis of prostatic cancer cells.
PTEN/MMAC1/TEP-1 (PTEN) tumor suppressor and androgen receptor play important roles in prostatic tumorigenesis by exerting opposite effects on homeostasis of prostatic epithelium. Here, we describe a mutual repression and selective dominance between PTEN and the androgen receptor (AR) in the growth and the apoptosis of prostatic cancer cells. On the one hand, PTEN and an inhibitor of phosphoinositide 3-kinase repressed the transcriptional activity of the AR as well as androgen-induced cell proliferation and production of prostate-specific antigen. On the other hand, androgens protected prostate cancer cells from PTEN-induced apoptosis in an AR-dependent manner. Whereas the repression of the transcriptional activity of the AR by PTEN is likely to involve the down-regulation of AKT, androgens protected prostate cancer cells from PTEN-induced apoptosis without an effect on AKT activity, demonstrating a differential involvement of AKT in the interaction between PTEN and the AR. Our data suggest that the loss of PTEN function may induce tumorigenesis through unopposed activity of the AR as well as contribute to the resistance of prostate cancers to androgen ablation therapy.
Department of Pathology, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center, Tampa, Florida 33612-4799, USA.
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D059002:Androgen Receptor Antagonists; D017209:Apoptosis; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051059:PTEN Phosphohydrolase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D059002:Androgen Receptor Antagonists; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011944:Receptors, Androgen; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human