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Female sex hormones activate HERV-K through the OCT4 transcription factor in T47D breast cancer cells.

Research paper by Tam Dang TD Nguyen, James J Davis, Roelle Adriene RA Eugenio, Yingguang Y Liu

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: AIDS research and human retroviruses



Abstract

Female sex hormones, the OCT4 transcription factor, and human endogenous retroviruses (HERVs) are all involved in the development of breast cancer. However, whether there are crosstalks between these factors to promote breast cancer is still unknown. Using the T47D human breast cancer cell line, we have found that estradiol and progesterone synergistically activate HERV-K through nuclear receptors. The progesterone receptor (isoform B) binds a progesterone response element in a long terminal repeat (LTR5HS) of HERV-K. There is another transcription factor-binding motif in the LTR, the OCT4 motif, which is required for the hormones to activate gene transcription downstream of the LTR. Gel shift assays and co-immunoprecipitation indicate that the progesterone receptor and the OCT4 transcription factor interact on the protein level. Methylation of the progesterone response element enhances binding of the progesterone receptor. These findings help to elucidate the previously unknown crosstalks among the sex hormones, OCT4, and HERVs in contributing to breast cancer proliferation and tumorigenesis that may be useful in guiding further development of cancer therapies.