Discipline: Biological Sciences
Subcategory: STEM Research
Saumya Ramanathan - Fisk University
Co-Author(s): Ashley Colemon and Richala Jackson, Fisk University; Taylor Harris, Washington University, St. Louis
Melanoma Antigen Genes (MAGEs) are a family of tumor-associated genes. MAGE-A, -B and -C genes belong to the Type I MAGE subfamily. They are typically expressed in the male germline and then aberrantly expressed in many cancers and therefore referred to as cancer-testis antigens. Their expression in tumors is often associated with poor patient prognosis. There is a significant gap in understanding the mechanisms that regulate the expression of Type I MAGE genes. While cancers often express more than one MAGE gene, this study focusses on MAGE-B2, an exemplary member of the Type I gene family and a bona fide cancer-testis antigen. We hypothesized that epigenetic mechanisms such as DNA methylation, which regulates the expression of many germline genes also regulates MAGE-B2 gene expression. Using DNA methyltransferase (DNMT) inhibitors and bioinformatics analysis of MAGE-B2 promoter, we have determined that while CpG methylation does regulate gene expression, remarkably, when “normal” cells are threatened with toxins and DNA damage they resort to expressing the MAGE-B2. In addition, we show that expressing MAGE-B2 provides non-transformed cells with a proliferative advantage and allows cells to grow in an anchorage-independent manner. Taken together our data indicate that cells use epigenetic memory to express MAGE-B2 resulting in shift of the cells’ gene signature to a pro-proliferative, anti-apoptotic state that firmly places cells in the path to transformation.
Funder Acknowledgement(s): NSF HBCU-UP Research Initiation Award HRD1764201 to S.R.
Faculty Advisor: None Listed,