G1P3, an interferon- and estrogen-induced survival protein contributes to hyperplasia, tamoxifen resistance and poor outcomes in breast cancer
G1P3, an interferon- and estrogen-induced survival protein contributes to hyperplasia, tamoxifen resistance and poor outcomes in breast cancer
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DOI：
10.1038/onc.2011.393
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发表时间：
2012-04-01
期刊：
影响因子：
8
通讯作者：
Borden, E. C.
中科院分区：
文献类型：
--
作者：
Cheriyath, V.;Kuhns, M. A.;Borden, E. C.
激素调节的生存因子在乳腺癌中起重要作用。在这里，我们阐明G1 P3，一种由干扰素（IFN）诱导的生存蛋白，作为雌激素信号传导的靶点，并导致雌激素受体阳性（ER+）乳腺癌的不良结局。与正常乳腺组织相比，G1 P3在恶性上皮中上调（高50倍），并由雌激素体外诱导。与其在早期乳腺癌（增生和导管原位癌）中的过表达雅阁，在形态发生测定中，G1 P3通过抑制增殖诱导的线粒体电位丧失和凋亡（失巢凋亡）来增强导致增生的MCF 10 A腺泡腔细胞的存活。在失巢凋亡的细胞中，G1 P3减弱了Bcl-2家族的促凋亡成员Bim蛋白的诱导，并逆转了Bcl-2蛋白的下调。下调G1 P3可诱导BT-549乳腺癌细胞自发凋亡，并显著抑制ER+乳腺癌细胞MCF 7的生长（P
Hormonally regulated survival factors can have an important role in breast cancer. Here we elucidate G1P3, a survival protein induced by interferons (IFNs), as a target of estrogen signaling and a contributor to poor outcomes in estrogen receptor-positive (ER+) breast cancer. Compared with normal breast tissue, G1P3 was upregulated in the malignant epithelium (50 x higher) and was induced by estrogen ex vivo. In accord with its overexpression in early stages of breast cancer (hyperplasia and ductal carcinoma in situ), in morphogenesis assays G1P3 enhanced the survival of MCF10A acinar luminal cells causing hyperplasia by suppressing detachment-induced loss of mitochondrial potential and apoptosis (anoikis). In cells undergoing anoikis, G1P3 attenuated the induction of Bim protein, a proapoptotic member of the Bcl-2 family and reversed the downmodulation of Bcl-2 protein. Downregulation of G1P3 induced spontaneous apoptosis in BT-549 breast cancer cells and significantly reduced the growth of ER+ breast cancer cell MCF7 (P