DNA Repair Genes PAXIP1 and TP53BP1 Expression is Associated with Breast Cancer Prognosis

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2017 May 6

PMID 28475402

Citations 13

Authors

Giuliana De Gregoriis

Juliene Antonio Ramos

Priscila Valverde Fernandes

Giselle Maria Vignal

Rafael Canfield Brianese

Dirce Maria Carraro

Alvaro N Monteiro

Claudio Jose Struchiner

Guilherme Suarez-Kurtz

Rosane Vianna-Jorge

Marcelo Alex de Carvalho

Affiliations

Soon will be listed here.

Abstract

Despite remarkable advances in diagnosis, prognosis and treatment, advanced or recurrent breast tumors have limited therapeutic approaches. Many treatment strategies try to explore the limitations of DNA damage response (DDR) in tumor cells to selectively eliminate them. BRCT (BRCA1 C-terminal) domains are present in a superfamily of proteins involved in cell cycle checkpoints and the DDR. Tandem BRCT domains (tBRCT) represent a distinct class of these domains. We investigated the expression profile of 7 tBRCT genes (BARD1, BRCA1, LIG4, ECT2, MDC1, PAXIP1/PTIP and TP53BP1) in breast cancer specimens and observed a high correlation between PAXIP1 and TP53BP1 gene expression in tumor samples. Tumors with worse prognosis (tumor grade 3 and triple negative) showed reduced expression of tBRCT genes, notably, PAXIP1 and TP53BP1. Survival analyses data indicated that tumor status of both genes may impact prognosis. PAXIP1 and 53BP1 protein levels followed gene expression results, i.e., are intrinsically correlated, and also reduced in more advanced tumors. Evaluation of both genes in triple negative breast tumor samples which were characterized for their BRCA1 status showed that PAXIP1 is overexpressed in BRCA1 mutant tumors. Taken together our findings indicate that PAXIP1 status correlates with breast cancer staging, in a manner similar to what has been characterized for TP53BP1.

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