Spencer Lea

Spencer Lea

PI: Jennifer Pietenpol, PhD , Department of Biochemistry

Exploration of Gain-Of-Function p53 Protein Mutations in  Triple Negative Breast Cancer

Previous research efforts have shown that, generally, cases of Triple-Negative Breast Cancer (TNBC) lack common oncogenic drivers, thus leading to worse outcomes on average for patients with TNBC than for those with breast cancer as a whole. Without known oncogenic drivers it is difficult to develop therapies that target specific mutations. However, research efforts have also shown that a majority of TNBC cases do include mutations in the p53 tumor suppressor (TP53) gene, resulting in the production of a protein with a single amino acid difference. The Pietenpol lab and others have identified special “gain of function” tumor-promoting properties conferred by missense mutant forms of p53, including increased cellular growth, genomic instability, and resistance to chemotherapeutic agents. Despite such properties having been described, their underlying mechanistic causes remain poorly understood. Prior experimentation has demonstrated that in vitro cell lines containing p53 point missense mutations have increased cell size and exhibit aneuploidy at an increased frequency as compared to wild type and null point mutation cell lines. To further elucidate these “gain-of-function” properties I will perform in-vitro clonal competition assays between wild-type, null, and missense p53 mutants. These assays will provide insight as to whether previously observed p53 missense phenotypes pertaining to metabolism will translate into increased survivability when in direct competition with wild-type and null cells.