Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance
Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance
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DOI：
10.1073/pnas.0407772101
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发表时间：
2005-01-04
影响因子：
11.1
通讯作者：
Donahoe, PK
中科院分区：
文献类型：
--
作者：
Renaud, EJ;MacLaughlin, DT;Donahoe, PK
苗勒管抑制物质（MIS）是TGF-β生物反应调节剂超家族的一种140 kDa同源二聚体糖蛋白，可导致发育中的男性胚胎苗勒管退化。MIS还可诱导卵巢癌和宫颈癌细胞系的生长停滞和凋亡。卵巢和子宫颈上皮的胚胎祖细胞是体腔上皮，在雄性中在MIS的指导下退化的相同组织。子宫内膜和子宫也起源于体腔上皮和苗勒管。在这里，我们表明，正常人子宫内膜和子宫内膜癌表达MIS的受体，MIS可以抑制一些人子宫内膜癌细胞系的增殖，表达MIS II型受体。在代表性的子宫内膜癌细胞系AN 3CA中，MIS影响关键细胞周期调控蛋白的表达。这项工作拓宽了MIS可能控制的肿瘤范围，并通过阐明MIS信号通路，确定了其他潜在的干预途径。
Mullerian Inhibiting Substance (MIS), a 140-kDa homodimer glycoprotein member of the TGF-beta superfamily of biological-response modifiers, causes regression of the Mullerian ducts in developing male embryos. MIS also can induce growth arrest and apoptosis in ovarian and cervical cancer cell lines. The embryonic progenitor of the ovarian and cervical epithelium is the coelomic epithelium, the same tissue that regresses under the direction of MIS in the male. The endometrium and uterus also arise from the coelomic epithelium and the Mullerian ducts. Here, we show that both normal human endometrium and endometrial cancers express the receptor for MIS and that MIS can inhibit the proliferation of a number of human endometrial cancer cell lines that express the MIS type II receptor. In the representative endometrial cancer cell line AN3CA, MIS affects the expression of key cell-cycle regulatory proteins. This work broadens the scope of tumors that MIS can potentially control and, by elucidating the MIS signaling pathway, identifies other potential avenues for intervention.