Estrogen receptor β inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest
Estrogen receptor β inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest
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DOI：
10.1158/0008-5472.can-03-2446
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发表时间：
2004-01-01
期刊：
影响因子：
11.2
通讯作者：
Leitman, DC
中科院分区：
文献类型：
--
作者：
Paruthiyil, S;Parmar, H;Leitman, DC
研究表明雌激素受体（ER）a介导雌激素的促乳腺癌作用。ER β在乳腺癌中的作用尚不清楚。阐明ER β在乳腺癌发病机制中的作用非常重要，因为许多人乳腺肿瘤同时表达ER α和ER β。我们发现腺病毒介导的ER β表达改变了ER α阳性MCF-7细胞的表型。雌激素增加细胞增殖并导致仅表达ER α的MCF-7细胞的肿瘤形成。相比之下，将ER β引入MCF-7细胞导致体外增殖抑制，并防止响应雌二醇的小鼠异种移植模型中的肿瘤形成。ER β通过抑制c-myc、细胞周期蛋白D1和细胞周期蛋白A基因转录，并增加p21（Cip 1）和p27（Kip 1）的表达，从而导致G（2）细胞周期停滞，从而抑制增殖。这些结果表明ER α和ER β在MCF-7细胞中对细胞增殖和肿瘤形成产生相反的作用。天然或合成的ER β选择性雌激素可能缺乏激素替代疗法中雌激素所表现出的乳腺癌促进特性，并且可能用于乳腺癌的化学预防。
Studies indicate that estrogen receptor (ER) a mediates breast cancer-promoting effects of estrogens. The role of ERbeta in breast cancer is unknown. Elucidating the role of ERbeta in the pathogenesis of breast cancer is important because many human breast tumors express both ERalpha and ERbeta. We show that adenovirus-mediated expression of ERbeta changes the phenotype of ERalpha-positive MCF-7 cells. Estradiol increases cell proliferation and causes tumor formation of MCF-7 cells expressing only ERalpha. In contrast, introducing ERbeta into MCF-7 cells causes an inhibition of proliferation in vitro and prevents tumor formation in a mouse xenograft model in response to estradiol. ERbeta inhibits proliferation by repressing c-myc, cyclin D1, and cyclin A gene transcription, and increasing the expression of p21(Cip1) and p27(Kip1), which leads to a G(2) cell cycle arrest. These results demonstrate that ERalpha and ERbeta produce opposite effects in MCF-7 cells on cell proliferation and tumor formation. Natural or synthetic ERbeta-selective estrogens may lack breast cancer promoting properties exhibited by estrogens in hormone replacement regimens and may be useful for chemoprevention of breast cancer.