Kub5-Hera ^RPRD1B Deficiency Promotes "BRCAness" and Vulnerability to PARP Inhibition in BRCA-proficient Breast Cancers.

ABSTRACT:

Purpose

Identification of novel strategies to expand the use of PARP inhibitors beyond BRCA deficiency is of great interest in personalized medicine. Here, we investigated the unannotated role of Kub5-Hera^RPRD1B (K-H) in homologous recombination (HR) repair and its potential clinical significance in targeted cancer therapy.

Experimental design

Functional characterization of K-H alterations on HR repair of double-strand breaks (DSB) were assessed by targeted gene silencing, plasmid reporter assays, immunofluorescence, and Western blots. Cell survival with PARP inhibitors was evaluated through colony-forming assays and statistically analyzed for correlation with K-H expression in various BRCA1/2 nonmutated breast cancers. Gene expression microarray/qPCR analy

SUBMITTER: Motea EA 

PROVIDER: S-EPMC6295248 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature