Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.
Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.
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DOI：
10.1371/journal.pone.0026250
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lee P
中科院分区：
文献类型：
--
作者：
Ligr M;Patwa RR;Daniels G;Pan L;Wu X;Li Y;Tian L;Wang Z;Xu R;Wu J;Chen F;Liu J;Wei JJ;Lee P
激素，包括雌激素和孕激素，及其受体在卵巢癌的发生和发展中起重要作用。雄激素及其受体和辅激活因子也参与了这些过程。p44/Mep50/WDR77被鉴定为甲基体复合物的亚基，并且最近被表征为类固醇受体共激活剂，其以配体依赖性方式增强雄激素受体以及雌激素受体介导的转录活性。我们先前描述了p44在前列腺癌、睾丸癌和乳腺癌中的不同表达和功能。在这份报告中，我们研究了p44在卵巢癌中的表达和功能。与前列腺癌和睾丸癌的发现相反，与乳腺癌相似，p44在形态正常的卵巢表面和输卵管上皮中显示出强烈的细胞质定位，而在浸润性卵巢癌中观察到核p44。我们观察到p44在卵巢细胞中可以作为雄激素受体（AR）和雌激素受体（ER）的共激活剂。此外，在雌激素或雄激素存在下，核定位的p44过表达刺激卵巢癌细胞的增殖和侵袭。这些发现有力地表明，p44在卵巢肿瘤发生过程中介导激素的作用。
Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.
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