A Novel Pathway That Links Caveolin-1 Down-Regulation to BRCA1 Dysfunction in Serous Epithelial Ovarian Cancer Cells

Overview

Journal Enliven Chall Cancer Detect Ther

Date 2015 Jan 17

PMID 25594072

Citations 3

Authors

Jingyao Xu

Stephanie Agyemang

Yunlong Qin

Kartik Aysola

Mercedes Giles

Gabriela Oprea

Ruth M ORegan

Edward E Partridge

Sandra Harris-Hooker

Valarie Montgomery Rice

E Shyam P Reddy

Veena N Rao

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer is the second most common gynecological cancer and the five-year survival rate is only about 40%. High-grade serous carcinoma is the pre-dominant histotype associated with hereditary ovarian cancer and women with inherited mutations in BRCA1 have a lifetime risk of 40-60%. BRCA1 and its isoform BRCA1a are multifunctional proteins that are the most evolutionary conserved of all the other splice variants. Our group has previously reported that BRCA1/1a proteins, unlike K109R and C61G mutants, suppress growth of ovarian cancer cells by tethering Ubc9. In this study we found wild type BRCA1/1a proteins to induce expression of caveolin-1, a tumor suppressor in BRCA1-mutant serous epithelial ovarian cancer (SEOC) cells by immunofluorescence analysis. The K109R and C61G disease associated mutant BRCA1 proteins that do not bind Ubc9 were not as efficient in up-regulation of caveolin-1 expression in SEOC cells. Additionally, immunofluorescence analysis showed BRCA1/1a proteins to induce redistribution of Caveolin-1 from cytoplasm and nucleus to the cell membrane. This is the first study demonstrating the physiological link between loss of Ubc9 binding, loss of growth suppression and loss of Caveolin-1 induction of disease-associated mutant BRCA1 proteins in SEOC cells. Decreased Caveolin-1 expression combined with elevated Ubc9 expression can in the future be used as an early biomarker for BRCA1 mutant SEOC.

Citing Articles

Different Role of Caveolin-1 Gene in the Progression of Gynecological Tumors.

Gong Y, Yang Y, Tian S, Chen H Asian Pac J Cancer Prev. 2019; 20(11):3259-3268.

PMID: 31759347 PMC: 7062999. DOI: 10.31557/APJCP.2019.20.11.3259.

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery.

Wang X, Liu Z, Yang Z BMC Urol. 2018; 18(1):102.

PMID: 30424755 PMC: 6234622. DOI: 10.1186/s12894-018-0418-4.

Molecular Mechanism Linking BRCA1 Dysfunction to High Grade Serous Epithelial Ovarian Cancers with Peritoneal Permeability and Ascites.

Desai A, Xu J, Aysola K, Akinbobuyi O, White M, Reddy V J Gynecol Res. 2015; 1(1).

PMID: 26665166 PMC: 4671517. DOI: 10.15744/2454-3284.1.103.

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