Benbrahim-Tallaa Lamia, Liu Jie, Webber Mukta M, Waalkes Michael P
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, NCI at NIEHS, Research Triangle Park, North Carolina 27709, USA.
Prostate. 2007 Feb 1;67(2):135-45. doi: 10.1002/pros.20479.
Lethal prostate cancers often become androgen-independent due to androgen receptor (AR) overexpression. The role of cadmium in prostate tumor progression was determined.
Control and cadmium-transformed prostate epithelial cells (CTPE) were compared for steroid-induced proliferation, steroid receptor expression, and androgen metabolism.
CTPE cells showed rapid proliferation in complete medium and sustained proliferation in steroid-reduced medium. Androgens stimulated significantly less cell proliferation and AR-related genes expression in CTPE cells. 5alpha-Dihydrotestosterone increased PSA expression more effectively in control cells. Flutamide reduced 5alpha-dihydrotestosterone-stimulated growth less effectively in CTPE cells compared to control. CTPE cells showed decreased p27 expression. Estrogen receptors were overexpressed and estradiol markedly stimulated proliferation in CTPE cells. In CTPE cells 5alpha-aromatase was markedly increased, while 5alpha-reductase was decreased.
Cadmium-induced malignant transformation stimulates androgen independence, unrelated to AR expression or activity. Increased estrogen receptor and 5alpha-aromatase expression suggest estrogen signaling may be critical to this process.
致死性前列腺癌常因雄激素受体（AR）过度表达而变得雄激素非依赖。本研究确定了镉在前列腺肿瘤进展中的作用。
比较对照和镉转化的前列腺上皮细胞（CTPE）在类固醇诱导的增殖、类固醇受体表达及雄激素代谢方面的差异。
CTPE细胞在完全培养基中显示快速增殖，在低类固醇培养基中持续增殖。雄激素刺激CTPE细胞增殖及AR相关基因表达的作用明显较弱。5α-双氢睾酮在对照细胞中更有效地增加前列腺特异抗原（PSA）表达。与对照相比，氟他胺在CTPE细胞中降低5α-双氢睾酮刺激生长的效果较差。CTPE细胞中p27表达降低。雌激素受体过度表达，雌二醇显著刺激CTPE细胞增殖。在CTPE细胞中，5α-芳香化酶显著增加，而5α-还原酶减少。
镉诱导的恶性转化促进雄激素非依赖，与AR表达或活性无关。雌激素受体和5α-芳香化酶表达增加提示雌激素信号通路可能对此过程至关重要。
