Over-expression of COX-2, which was detected in endometrial carcinoma, stimulated the proliferation and angiogenesis of cancer cell [16]. COX-2 also is an important rate-limiting enzyme
in prostaglandin synthesis [13]. The endometrial prostaglandin E2 induced the activity of aromatase (P450arom) by up-regulating intracellular cAMP levels in endometrial stromal cells. COX-2 indirectly regulated the expression of P450arom by influencing the synthesis of PGE2[17]. P450arom is the rate-limiting enzyme catalyzing the final step in the conversion from androgen to estrogen. P450arom determined the levels of estrogen in normal and abnormal tissues directly, which maintained ACP-196 concentration the estrogen-related
HDAC inhibitor physiologic functions and impacted the pathogenesis and prognosis of estrogen-dependent diseases [18]. High levels of HER-2/neu have been detected in endometrial carcinoma tissues and were found to correlate with tumor malignancy [19–21]. Our results suggested that HER-2/neu, as a potential upstream regulatory molecule in the COX-2/PGE2/P450arom signaling pathway, could play a critical role in estrogen-dependent endometrial carcinoma. These findings provided an improved understanding of the molecular mechanisms of estrogen-dependent endometrial carcinoma, and might instruct to screen the targets for hormone-dependent gynecologic tumors related to HER-2/neu. Acknowledgement This study was supported by NVP-LDE225 price grants from the National Natural Science Foundation of China (No. 81272874), the Project from Educational
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