Volume 17, No 10, Oct 2007
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 17 Issue 10, October 2007: 869-880
ORIGINAL ARTICLES
Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin
Yuan Guang Meng1, Wei Dong Han2, Ya Li Zhao2, Ke Huang1, Yi Ling Si2, Zhi Qiang Wu2 and Yi Ming Mu3
1Department of Obstetrics and Gynecology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China;
2Department of Molecular Biology, The Institute of Basic Medicine, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China;
3Department of Endocrinology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China
Correspondence: Wei Dong Han(hanwdrsw69@yahoo.com)
LRP16 was previously identified as an estrogen-induced gene in breast cancer cells. The responsiveness of LRP16 to estrogen and its functional effects in endometrial cancer (EC) cells are still unclear. Here, we show that the mRNA level and promoter activity of the
LRP16 gene were significantly increased by 17β-estradiol (E2) in estrogen receptor α (ERα)-positive Ishikawa human EC cells. Although the growth rate of Ishikawa cells was not obviously affected by ectopic expression of LRP16, the results of a Transwell assay showed an approximate one-third increase of the invasive capacity of LRP16-overexpressing cells. As a result of molecular screening, we observed that the expression of E-cadherin, an essential adhesion molecule associated with tumor metastasis, was repressed by LRP16. Further promoter analyses demonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner. However, the inhibition was abolished by estrogen deprivation, indicating that the downregulation of E-cadherin transcription by LRP16 requires ERα mediation. Chromatin immunoprecipitation analyses revealed that the binding of ERα to the E-cadherin promoter was antagonized by LRP16, suggesting that LRP16 could interfere with ERα-mediated transcription. These results suggest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin in human ECs.
Cell Research (2007) 17:869-880. doi: 10.1038/cr.2007.79; published online 25 September 2007
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