Melanoma Antigen Genes (MAGEs) are defined as cancer-testis antigens due to their unique expression pattern. There are two families of MAGEs, Type I and Type II. Type I MAGEs are expressed in the testis and in no other normal somatic tissue and then re-expressed in many cancers. Type II MAGEs on the other hand, are ubiquitous in their expression. . The MAGE-A family are members of the type 1 family located on the X chromosome. Type I MAGEs, considered to be true cancer-testis antigens are all located on the X chromosome. Previous studies show that reversible DNA methylation of CpG sites upstream of MAGE-A promoters regulates their expression. Many members of the MAGE1 subfamily cause increase in proliferative phenotypes. However, MAGEA5 and MAGEA10 expressing cells, demonstrated resistance to high doses of chemotherapeutic agent 5-flurouracil. We aim to understand the mechanism behind this resistance. We will perform RNA-Sequencing on cells expressing MAGEA5/A10 and control cells and determine protein binding partners of MAGEA5/A10 using IP-Mass Spectrometry. In addition, we will test the hypothesis that in the heterogenous tumor cell population, MAGEA5/A10 is expressed in the cancer "stem cells" and that is responsible for driving chemo-resistance. We will also test resistance of these cells to other chemotherapeutic agents such as taxols.
NSF HBCU UP: Research Initiation Award HRD1764201 to S.R.
