Androgen receptor expression in prostate carcinoma cells suppresses α6β4 integrin-mediated invasive phenotype
Androgen receptor expression in prostate carcinoma cells suppresses α6β4 integrin-mediated invasive phenotype
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DOI：
10.1210/en.141.9.3172
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发表时间：
2000-09-01
期刊：
影响因子：
4.8
通讯作者：
Baldi, E
中科院分区：
文献类型：
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作者：
Bonaccorsi, L;Carloni, V;Baldi, E
前列腺癌细胞在雄激素消融治疗后可能失去雄激素敏感性，变得高度侵袭和转移。雄激素非依赖性前列腺癌较高致瘤性的生物学机制尚不完全清楚。我们证明雄激素受体通过调节α 6 β 4整合素的表达来调节前列腺癌细胞的粘附和侵袭可能是这种现象的分子机制之一。我们发现，α 6和β 4亚基的蛋白质和基因表达强烈减少，在雄激素敏感的细胞系LNCaP相对于雄激素非依赖性的PC 3和PC 3细胞与全长雄激素受体表达载体的转染导致α 6 β 4整合素的表达减少，减少粘附层粘连蛋白，并抑制基质胶侵袭。雄激素受体阳性的PC3克隆在软琼脂中的生长也受到抑制。用合成雄激素R1881处理雄激素受体阳性克隆进一步降低α 6和β 4信使RNA表达以及对层粘连蛋白的粘附和基质胶侵袭。我们的研究结果表明，雄激素通过调节整合素的表达和功能来调节细胞与细胞外基质的粘附和侵袭，从而保持前列腺癌细胞的低侵袭表型。
Prostate cancer cells may lose androgen-sensitivity after androgen ablation therapy, becoming highly invasive and metastatic. The biological mechanisms responsible for higher tumurogenicity of androgen-independent prostate carcinomas are not entirely known. We demonstrate that androgen receptor regulation of adhesion and invasion of prostate cancer cells through modulation of alpha 6 beta 4 integrin expression may be one of the molecular mechanisms responsible of this phenomenon. We found that protein and gene expressions of alpha 6 and beta 4 subunits were strongly reduced in the androgen-sensitive cell line LNCaP respect to the androgen-independent PC3 and that transfection of PC3 cells with a full-length androgen receptor expression vector resulted in a decreased expression of alpha 6 beta 4 integrin, reduced adhesion on laminin, and suppressed Matrigel invasion. Growth in soft agar was also suppressed in androgen receptor-positive PC3 clones. Treatment of androgen receptor positive clones with the synthetic androgen R1881 further reduced alpha 6 and beta 4 messenger RNA expression as well as adhesion on laminin and Matrigel invasion. Our results indicate that androgens regulate cell-extracellular matrix adhesion and invasion by modulation of integrin expression and function, thus keeping a low invasive phenotype of prostate cancer cells.