Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis

Huijian Wu, Yupeng Chen, Jing Liang, Bin Shi, Ge Wu, Ying Zhang, Dan Wang, Ruifang Li, Xia Yi, Hua Zhang, Luyang Sun, Yongfeng Shang

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

Tamoxifen, a selective oestrogen receptor modulator, has been used in the treatment of all stages of hormone-responsive breast cancer. However, tamoxifen shows partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial cancer. The molecular explanation for these observations is not known. Here we show that tamoxifen and oestrogen have distinct but overlapping target gene profiles. Among the overlapping target genes, we identify a paired-box gene, PAX2, that is crucially involved in cell proliferation and carcinogenesis in the endometrium. Our experiments show that PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, and that this activation is associated with cancer-linked hypomethylation of the PAX2 promoter.

Original languageEnglish (US)
Pages (from-to)981-987
Number of pages7
JournalNature
Volume438
Issue number7070
DOIs
StatePublished - Dec 15 2005

ASJC Scopus subject areas

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    Wu, H., Chen, Y., Liang, J., Shi, B., Wu, G., Zhang, Y., Wang, D., Li, R., Yi, X., Zhang, H., Sun, L., & Shang, Y. (2005). Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature, 438(7070), 981-987. https://doi.org/10.1038/nature04225