A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase
A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase
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DOI：
10.1038/6495
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发表时间：
1999-03-01
期刊：
影响因子：
82.9
通讯作者：
Sawyers, CL
中科院分区：
文献类型：
--
作者：
Craft, N;Shostak, Y;Sawyers, CL
前列腺癌从激素敏感的雄激素依赖性阶段发展为激素难治性，雄激素独立的肿瘤。尽管抗雄激素治疗，但雄激素受体途径在这些与雄激素无关的肿瘤中起作用。在我们的LAPC-4前列腺癌模型中，与雄激素依赖性的同伴相比，雄激素非依赖性的subline表示HER-2/NEU受体酪氨酸激酶的水平更高。在雄激素依赖性前列腺癌细胞中强迫HER-2/NEU的过度表达允许配体无关的生长。在没有配体的情况下，HER-2/NEU激活了雄激素受体途径，并与低水平的雄激素协同以“超激活”途径。通过调节对低剂量雄激素的反应，酪氨酸激酶受体可以恢复雄激素受体功能以使前列腺癌细胞与前列腺癌的临床进展直接相关。
Prostate cancer progresses from a hormone-sensitive, androgen-dependent stage to a hormone-refractory, androgen-independent tumor. The androgen receptor pathway functions in these androgen-independent tumors despite anti-androgen therapy. In our LAPC-4 prostate cancer model, androgen-independent sublines expressed higher levels of the HER-2/neu receptor tyrosine kinase than their androgen-dependent counterparts. Forced overexpression of HER-2/neu in androgen-dependent prostate cancer cells allowed ligand-independent growth. HER-2/neu activated the androgen receptor pathway in the absence of ligand and synergized with low levels of androgen to 'superactivate' the pathway. By modulating the response to low doses of androgen, a tyrosine kinase receptor can restore androgen receptor function to prostate cancer cells, a finding directly related to the clinical progression of prostate cancer.