Endogenous Retroviruses and Breast Carcinoma Development.
Abstract
Human endogenous retroviruses (HERVs) have been implicated in the etiology of neoplasia including breast cancer. Like other transposable elements, their intracellular transposition may play an important role in DNA mutagenesis and carcinogenesis. To gain insight into the role of HERV in carcinogenesis, we have examined the mechanism of expression of a HERV family, HERV-K, in T47D. breast tumor cell line as active expression is a prerequisite step in transposition-mediated mutagenesis by HERV. We show that HBRV-K expression is enhanced by steroid hormones and that an unique set of HERV-K elements containing progesterone response element (PRE) is selectively activated by the hormones. We further showed that the PRE in the viral promoter is an effective enhancer element and the ER and progesterone receptor (PR) in T47D cells are effective transcription activators. The results suggest that these parameters are responsible for the hormone-responsive HBRV-K expression. Prognosis of breast cancers is associated with their ability to respond to hormone treatment. Thus, hormone-specific HERV-K expression may be a useful prognostic marker for the progression of tumors to a hormone-resistant aggressive state.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1996
- Accession Number
- ADB218946
Entities
People
- Chin Howe
Organizations
- University of Pennsylvania