PARADOXICAL REGULATION OF ESTROGEN-DEPENDENT GROWTH-FACTOR GENE-EXPRESSION IN ESTROGEN-RECEPTOR (ER)-NEGATIVE HUMAN BREAST-CANCER CELLS STABLY EXPRESSING ER
PARADOXICAL REGULATION OF ESTROGEN-DEPENDENT GROWTH-FACTOR GENE-EXPRESSION IN ESTROGEN-RECEPTOR (ER)-NEGATIVE HUMAN BREAST-CANCER CELLS STABLY EXPRESSING ER
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DOI：
10.1016/0304-3835(94)90001-9
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发表时间：
1994-07-29
期刊：
影响因子：
9.7
通讯作者：
JORDAN, VC
中科院分区：
文献类型：
--
作者：
JENG, MH;JIANG, SY;JORDAN, VC
我们先前已经证明，用正义组成型野生型ER表达载体转染雌激素受体（ER）阴性人乳腺癌MDA-MP-231（克隆10A）细胞重新获得激素响应性（Jiang和Jordan，J. Natl. Chem.癌症研究所，84（1992）580-591）。因此，我们进行了研究，使用稳定的转染S30细胞，以确定ER在调节生长因子mRNA的水平，一个事件被认为是通过ER介导的，是重要的旁分泌和自分泌调节乳腺癌细胞增殖的功能。北方印迹分析显示17 β-雌二醇（E（2））可增加TGF α mRNA的表达，降低TGF β 2 mRNA的表达。ER对S30细胞TGF β 1和TGF β 3 mRNA水平无明显影响。添加抗雌激素ICI 164，384阻断了E2对TGF α和TGF β 2 mRNA水平的调节。在亲本MDA-MB-231 10A和反义ER转染子AS 23细胞中，这些生长因子mRNA的表达不受E（2）或ICI 164，384的影响。我们证明，在以前ER阴性的人乳腺癌细胞中ER的表达可以恢复E对生长因子mRNA表达的调节（2）。TGF α的增加和TGF β 2的减少与激素应答细胞生长的增加有关。特别地，转染的细胞响应于雌激素而具有降低的生长。此外，这些数据表明，除了ER外，E还需要其他因子来调节TGF β 1和TGF β 3基因（2）。
We have previously demonstrated that transfection of estrogen receptor (ER)-negative human breast cancer MDA-MP-231 (clone 10A) cells with a sense constitutive wildtype ER expression vector regains hormonal responsiveness (Jiang and Jordan, J. Natl. Cancer Inst., 84 (1992) 580-591). We have therefore undertaken studies using stable transfectant S30 cells to determine the function of ER in the regulation of the levels of growth factor mRNAs, an event believed to be mediated via the ER and is important for the paracrine and autocrine regulation of breast cancer cell proliferation. Northern blot analysis demonstrated that 17 beta-estradiol (E(2)) increased the level of TGF alpha mRNA and decreased the level of TGF beta 2 mRNA. TGF beta 1 and TGF beta 3 mRNA levels were not affected by ER in S30 cells. The addition of anti-estrogen ICI 164,384 blocked the regulation of the mRNA levels of TGF alpha and TGF beta 2 by E2. The expression of these growth factor mRNAs was not affected by E(2) or ICI 164,384 in the parental MDA-MB-231 10A and antisense ER transfectant AS23 cells. We demonstrated that the expression of ER in previously ER-negative human breast cancer cells can restore the regulation of growth factor mRNA expression by E(2). An increase in TGF alpha and a decrease in TGF beta 2 is associated with an increase in growth of hormone responsive cells. Paradoxically the transfected cells have decreased growth in response to estrogen. Furthermore, these data suggest that other factors in addition to ER are required for TGF beta 1 and TGF beta 3 gene regulation by E(2).