el-Tanani M K, Green C D
Department of Biochemistry, University of Liverpool, UK.
Mol Cell Endocrinol. 1995 Apr 28;111(1):75-81. doi: 10.1016/0303-7207(95)03550-q.
The level of oestrogen-responsive gene expression in breast tumours has been proposed as a predictor of the response of the tumour to endocrine (anti-oestrogen) therapy. We demonstrate that different oestrogen-responsive genes may differ in their responses to other hormones. pLIV-1 and pS2 are two oestrogen-regulated genes that are expressed in the MCF-7 human breast cancer cell line. We show that pLIV-1 mRNA, but not pS2 mRNA, is also induced, to a lesser extent, by progesterone, 5 alpha-dihydrotestosterone and dexamethasone. For pLIV-1, combinations of these hormones with oestradiol and with the pure anti-oestrogen, ICI 164384, indicate that the mechanism of its response to these other steroid hormones is clearly separable from its response to oestrogen. Such behaviour in breast tumours in vivo could explain the lack of absolute correlation between marker gene expression and anti-oestrogen sensitivity and between the expression of individual marker genes.
乳腺肿瘤中雌激素反应性基因的表达水平已被提议作为肿瘤对内分泌(抗雌激素)治疗反应的预测指标。我们证明,不同的雌激素反应性基因对其他激素的反应可能不同。pLIV-1和pS2是在MCF-7人乳腺癌细胞系中表达的两个雌激素调节基因。我们发现,孕酮、5α-二氢睾酮和地塞米松也能在较小程度上诱导pLIV-1 mRNA的表达,但不能诱导pS2 mRNA的表达。对于pLIV-1,这些激素与雌二醇以及与纯抗雌激素ICI 164384的组合表明,其对这些其他甾体激素反应的机制明显不同于其对雌激素的反应。体内乳腺肿瘤中的这种行为可以解释标记基因表达与抗雌激素敏感性之间以及各个标记基因表达之间缺乏绝对相关性的原因。