Mutant p53 gain of function induces HER2 over-expression in cancer cells

Abstract

[...]we evaluated the interaction of the p53 mutants over the HER2 receptor promoter. The presence of these point mutations radically alters p53 function causing not only a simple loss of wild-type function, but also a dominant negative effect by binding and inhibiting wtp53 or a Gain of Function (GOF) acquiring novel activities independent of wtp53 [3]. p53 GOF mutations have been shown to result in oncogenic and a major proliferative processes such as increased tumorigenicity, anchorage independent cell growth and increased growth rate, increased metastasis and invasiveness, decreased sensitivity to chemotherapeutic drugs, disruption of the spindle checkpoint, activated topoisomerase I activity and induction of gene amplification, reviewed in [3]. Taken together, these results suggest that both the p53R248Q and p53R273C mutants are directly involved in HER2 promoter activation. [...]both p53 mutants are contributing to the modification of the HER2 promoter towards a more activated chromatin by enriching H3 and H4 acetylation marks. Due to AARR’s role as first author, this implies a direct role of CONACYT in design, collection, analysis and interpretation of the data. [...]other grants obtained from CONACyT (168896) to Díaz-Chávez J and (236767) to Gariglio P were used for this work.