Steroid-independent activation of androgen receptor in androgen-independent prostate cancer - A possible role for the MAP kinase signal transduction pathway?
Steroid-independent activation of androgen receptor in androgen-independent prostate cancer - A possible role for the MAP kinase signal transduction pathway?
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DOI：
10.1016/s0303-7207(97)00168-8
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发表时间：
1997-10-31
影响因子：
4.1
通讯作者：
Liu, JP
中科院分区：
文献类型：
--
作者：
Zhu, X;Liu, JP
前列腺癌的内分泌治疗基于雄激素依赖。虽然雄激素去除的初始治疗效果很高，但雄激素非依赖性细胞的出现是不可避免的。体外研究表明，癌细胞在长期剥夺该类类固醇后也对特定类固醇激素无反应[1]。例如，在不存在雄激素的情况下孵育雄激素敏感性Shionogi小鼠乳腺癌细胞15天，随后对雄激素的生长促进作用完全耐受[2]。最初依赖雄激素的癌细胞在生长方面对雄激素的需求被解除的关键分子机制在很大程度上是未知的。雄激素受体（AR）的缺失可能清楚地成为这种变化的基础。然而，使用抗AR抗体的免疫组织学研究显示，在应答性和耐药性癌症中均存在AR [3，4]。此外，雄激素敏感的LNCaP前列腺癌细胞在缺乏雄激素的情况下的长期生长产生了雄激素不敏感的亚系;在从雄激素敏感到雄激素不敏感的转变过程中，
Endocrine therapy for prostate cancer is based on androgen dependence. Although the initial therapeutic efficacy of androgen ablation is high, the emergence of androgen-independent cells is inevitable. In vitro studies have shown that cancer cells also become unresponsive to a particular steroid hormone following prolonged deprivation of that class of steroid [1]. For example, incubation of androgen-sensitive Shionogi mouse mammary carcinoma cells for 15 days in the absence of androgens is followed by complete resistance to the growth promoting effects of androgens [2]. The critical molecular mechanisms, by which the originally androgen-dependent cancer cells are relieved of the requirement for androgens in terms of growth, are largely unknown.Loss of androgen receptors (AR) could clearly underlie such a change. Immunohistological studies using anti-AR antibodies, however, show the presence of AR in both responsive and resistant cancers [3, 4]. Moreover, long-term growth of androgen-sensitive LNCaP prostate cancer cells in the absence of androgens has produced an androgen-insensitive subline; during the transition from androgen-sensitive to androgen-insensi-