Characterization of mutant p53-based molecular mechanisms of tumor aggressiveness

DI BENEDETTO CAROLINA; BORINI CARLA; GIRARDINI J.E.

Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

Most human cancers often inactivate p53 through missense mutations in its DNA binding domain, leading to the expression of full-length point mutants, which not only lose the tumor suppressor function of the wt protein but also may acquire novel activities (gain of function-GOF), that promote aggressiveness and metastasis, as was proved by mouse models and in vitro data.We have previously found through microarrays that mutant p53 alters gene expression profile in MDA-MB-231 cancer cells. In particular, this change is associated with the development of aggressive breast tumors. We confirmed by Real Time PCR that a group of genes is upregulated and other is downregulated; we hypothesized both expression levels are associated to oncogenic functions. Within these groups, there are genes whose function was related to tumoral mechanisms, such as ICMT and AKR1B1, as well as genes whose relationship with cancer has been less studied. In order to study the role of these genes in tumoral development, we generated stable cell lines overexpressing the full-length proteins. Tumorigenic assays show that these proteins operate via different mechanisms leading to cancer.