Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor.
Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor.
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DOI：
10.1210/endo.138.4.5047
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发表时间：
1997-04
期刊：
影响因子：
4.8
通讯作者：
J. Szelei;J. Jimenez;A. Soto;M. F. Luizzi;C. Sonnenschein
中科院分区：
文献类型：
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作者：
J. Szelei;J. Jimenez;A. Soto;M. F. Luizzi;C. Sonnenschein
性类固醇通过两种不同的途径控制其靶细胞的增殖：1)增殖反应（step1）；2)抑制细胞增殖（step2）。细胞增殖调控机制尚不完全清楚；然而，人们普遍认为性类固醇受体在控制性类固醇靶细胞的增殖中起着重要作用。为了验证这一假设，将一个完整的人雄激素受体（AR）载体转染到人乳腺癌MCF7细胞中。稳定表达AR的克隆细胞称为MCF7- ar1细胞，其含有的AR大约是其衍生的野生型MCF7细胞的5倍。当将雌激素添加到10%炭葡聚糖剥离的人血清中时，这些ar转染的细胞保持了增殖能力，但当将雄激素添加到该培养基中时，这些细胞没有获得增殖能力。在无血清培养基（ITDME）中，这些细胞增殖最快，与MCF7细胞一样；然而，天然和合成雄激素阻止ar转染的细胞增殖。在ITDME中加入生理雄激素浓度（1 nM）对细胞增殖有抑制作用；这种作用几乎完全被合成雄激素拮抗剂Casodex逆转。在ITDME中添加雄激素的作用下，MCF7-AR1细胞在24 h内被阻滞在G0/G1期。这些数据表明：1)雄激素诱导的细胞增殖抑制（步骤2）是ar介导的；2) AR可能是必要的，但不是充分的，介导雄激素诱导的增殖反应（步骤1）。
Sex steroids control the proliferation of their target cells through two different pathways: 1) proliferative response (Step-1); and 2) inhibition of cell proliferation (Step-2). Mechanisms of cell proliferation regulation are incompletely understood; however, there is general agreement with the notion that sex steroid receptors play an important role in the control of the proliferation of sex steroid target cells. To test this hypothesis, a full human androgen receptor (AR) vector was transfected into human breast cancer MCF7 cells. The cloned cells that stably express the AR, called MCF7-AR1 cells, contained approximately five times more AR than the wild-type MCF7 cells from which they were derived. These AR-transfected cells retained their capacity to proliferate when estrogens were added to 10% charcoal-dextran stripped human serum but did not acquire the ability to proliferate when androgens were added to this medium. In serumless medium (ITDME), these cells proliferated maximally, as MCF7 cells did; however, natural and synthetic androgens prevented the AR-transfected cells from proliferating. Inhibition of cell proliferation occurred when physiological androgen concentrations (1 nM) were added to ITDME; this effect was almost completely reversed by Casodex, a synthetic androgen antagonist. Under the effect of androgens added to ITDME, MCF7-AR1 cells were arrested in the G0/G1 phase within 24 h. These data suggest that: 1) the androgen-induced inhibition of cell proliferation (Step-2) is AR-mediated; and 2) the AR may be necessary, but not sufficient, to mediate the androgen-induced proliferative response (Step-1).