Wu Z, Conaway M, Gioeli D, Weber M J, Theodorescu D
Department of Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Prostate. 2006 Jul 1;66(10):1114-23. doi: 10.1002/pros.20447.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is lost as a function of prostate tumor androgen dependence. While the transcriptional activity of the androgen receptor (AR) is inhibited by PTEN in androgen sensitive prostate cancer (CaP), the role of PTEN in androgen disease is unclear.
We developed a system where PTEN can be conditionally re-expressed at physiologic levels into a PTEN null metastatic human CaP cell line, C4-2, and androgen responsiveness examined.
PTEN induction reduces cell growth and blocks the growth effect of synthetic androgen R1881. The anti-androgen Casodex enhances the growth-inhibitory action of PTEN and this effect is independent of Akt phosphorylation. Combined PTEN induction and Casodex, result in a further decrease in prostate specific antigen promoter activity compared to PTEN but not Casodex alone.
PTEN induction confers androgen independent CaP cells enhanced responsiveness to the anti-proliferative effects of anti-androgens and this action may involve non-AR mediated effects.
10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）随着前列腺肿瘤雄激素依赖性而缺失。在雄激素敏感的前列腺癌（CaP）中，PTEN抑制雄激素受体（AR）的转录活性，但PTEN在雄激素疾病中的作用尚不清楚。
我们构建了一个系统，可将PTEN以生理水平条件性重新表达至PTEN缺失的转移性人CaP细胞系C4-2中，并检测雄激素反应性。
PTEN诱导可降低细胞生长并阻断合成雄激素R1881的生长效应。抗雄激素药物比卡鲁胺增强了PTEN的生长抑制作用，且这种效应与Akt磷酸化无关。与单独使用PTEN或比卡鲁胺相比，联合诱导PTEN和比卡鲁胺可导致前列腺特异性抗原启动子活性进一步降低。
PTEN诱导使雄激素非依赖性CaP细胞对抗雄激素的抗增殖作用反应性增强，且这种作用可能涉及非AR介导的效应。
