Li P, Nicosia S V, Bai W
Department of Pathology, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center, Tampa, Florida 33612-4799, USA.
J Biol Chem. 2001 Jun 8;276(23):20444-50. doi: 10.1074/jbc.M010226200. Epub 2001 Mar 16.
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.
PTEN/MMAC1/TEP-1（PTEN）肿瘤抑制因子和雄激素受体通过对前列腺上皮细胞稳态产生相反作用，在前列腺肿瘤发生过程中发挥重要作用。在此，我们描述了PTEN与雄激素受体（AR）在前列腺癌细胞生长和凋亡过程中的相互抑制及选择性优势。一方面，PTEN和磷酸肌醇3激酶抑制剂可抑制AR的转录活性以及雄激素诱导的细胞增殖和前列腺特异性抗原的产生。另一方面，雄激素以AR依赖的方式保护前列腺癌细胞免受PTEN诱导的凋亡。虽然PTEN对AR转录活性的抑制可能涉及AKT的下调，但雄激素保护前列腺癌细胞免受PTEN诱导的凋亡，而对AKT活性无影响，这表明AKT在PTEN与AR相互作用中的参与存在差异。我们的数据表明，PTEN功能丧失可能通过AR的无对抗活性诱导肿瘤发生，也可能导致前列腺癌对雄激素剥夺治疗产生抗性。
