Discipline: Biological Sciences
Subcategory: STEM Research
Saumya Ramanathan - Fisk University
Co-Author(s): Ashley Colemon, Angelle Jones; Department of Life and Physical Sciences, Fisk University
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 MAGEB2, an exemplary member of the Type I gene family and a bona fide cancer-testis antigen. Using DNA methyltransferase (DNMT) inhibitors and bioinformatics analysis of MAGEB2 promoter, we have discovered that while CpG methylation regulates the expression of MAGEB2, transcription factor JunD is recruited to the MAGEB2 promoter in cells expressing this gene. Remarkably, when normal cells are threatened with toxins and DNA damage, they resort to expressing the MAGEB2. In addition, we have discovered that expressing MAGE-B2 provides non-transformed cells with a proliferative advantage and allows cells to grow in an anchorage-independent manner by dampening TGF? signaling. Taken together our data indicate that MAGEB2 is a single gene driver of cellular transformation.
Funder Acknowledgement(s): NSF HBCU-UP Research Initiation Award HRD1764201 to S.R.
Faculty Advisor: None Listed,
NSF Affiliation: HBCU-UP