Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis.
Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis.
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DOI：
10.1158/0008-5472.can-10-1238
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发表时间：
2010-11-01
期刊：
影响因子：
11.2
通讯作者：
Horwitz KB
中科院分区：
文献类型：
--
作者：
Spillman MA;Manning NG;Dye WW;Sartorius CA;Post MD;Harrell JC;Jacobsen BM;Horwitz KB
Menopausal estrogen (E2) replacement therapy increases the risk of estrogen receptor (ER)-positive epithelial ovarian cancers (EOC). Whether E2 is tumorigenic or promotes expansion of undiagnosed pre-existing disease is unknown. To determine E2 effects on tumor promotion, we developed an intraperitoneal mouse xenograft model using ZsGreen fluorescent ER− 2008 and ER+ PEO4 human EOC cells. Tumor growth was quantified by in vivo fluorescent imaging. In ER+ tumors, E2 significantly increased size, induced progesterone receptors, and promoted lymph node metastasis, confirming that ER are functional and foster aggressiveness. Laser captured human EOC cells from ER− and ER+ xenografted tumors were profiled for expression of E2-regulated genes. Three classes of E-regulated EOC genes were defined, but less than 10% were shared with E-regulated breast cancer genes. Since breast cancer selective ER modulators (SERMs) are therapeutically ineffective in EOC, we suggest that our EOC-specific E-regulated genes can assist pharmacologic discovery of ovarian targeted SERM.
