Endometrial Cancers With Activating KRas Mutations Have Activated Estrogen Signaling and Paradoxical Response to MEK Inhibition.

ABSTRACT:

Objectives

The aims of this study were to determine if activating KRas mutation alters estrogen signaling in endometrial cancer (EC) and to explore the potential therapeutic impact of these alterations.

Methods

The Cancer Genome Atlas was queried for changes in estrogen-regulated genes in EC based on KRas mutation status. In vitro studies were conducted to evaluate estrogen receptor α (ERα) phosphorylation changes and related kinase changes in KRas mutant EC cells. The resulting effect on response to MEK inhibition, using trametinib, was evaluated. Immunohistochemistry was performed on KRas mutant and wild-type EC tumors to test estrogen signaling differences.

Results

KRas mutant tumors in The Cancer Genome Atlas showed decreased progesterone receptor expression (P =

SUBMITTER: Ring KL 

PROVIDER: S-EPMC5438270 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature