Histone Demethylase GASC1 as a Therapeutic Target in Basal breast cancer
Abstract
Previously, mapping of the 9p23-24 amplicon in esophageal cancer cell lines led us to the positional cloning of GASC1 which encodes a histone demethylase. However, the transforming roles of GASC1 in breast cancer remain to be determined. In this study, we identified GASC1 as one of the amplified genes for the 9p23-24 region in breast cancer, particularly in basal-like subtypes. Our in vitro assays demonstrated that increased expression of GASC1 induces transformed phenotypes, including growth factor-independent proliferation, anchorage independent growth, altered morphogenesis in Matrigel, and mammosphere forming ability, when over expressed in immortalized, nontransformed mammary epithelial MCF10A cells. Additionally, GASC1 demethylase activity may be linked to the stem cell phenotypes in breast cancer. Thus, GASC1 is a driving oncogene in the 9p23-24 amplicon in human breast cancer and targeted inhibition of GASC1 histone demethylase in cancer could provide potential new avenues for therapeutic development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA534910
Entities
People
- Zeng-quan Yang
Organizations
- Wayne State University