BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine

Show full item record



Permalink

http://hdl.handle.net/10138/164700

Citation

Gu , Y , Helenius , M , Vaananen , K , Bulanova , D , Saarela , J , Sokolenko , A , Martens , J , Imyanitov , E & Kuznetsov , S 2016 , ' BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine ' , Scientific Reports , vol. 6 , 28217 . https://doi.org/10.1038/srep28217

Title: BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine
Author: Gu, Yuexi; Helenius, Mikko; Vaananen, Kristiina; Bulanova, Daria; Saarela, Jani; Sokolenko, Anna; Martens, John; Imyanitov, Evgeny; Kuznetsov, Sergey
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-06-17
Language: eng
Number of pages: 9
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/164700
Abstract: Germ-line or somatic inactivation of BRCA1 is a defining feature for a portion of human breast cancers. Here we evaluated the anti-proliferative activity of 198 FDA-approved and experimental drugs against four BRCA1-mutant (HCC1937, MDA-MB-436, SUM1315MO2, and SUM149PT) and four BRCA1-wild-type (MDA-MB-231, SUM229PE, MCF10A, and MCF7) breast cancer cell lines. We found that all BRCA1-mutant cell lines were insensitive to inhibitors of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) Selumetinib and Pimasertib in contrast to BRCA1-wildtype control cell lines. However, unexpectedly, only two BRCA1-mutant cell lines, HCC1937 and MDA-MB-436, were hypersensitive to a nucleotide analogue 6-thioguanine (6-TG). SUM149PT cells readily formed radiation-induced RAD51-positive nuclear foci indicating a functional homologous recombination, which may explain their resistance to 6-TG. However, the reason underlying 6-TG resistance of SUM1315MO2 cells remains unclear. Our data reveal a remarkable heterogeneity among BRCA1-mutant cell lines and provide a reference for future studies.
Subject: DNA-DAMAGE RESPONSE
EMBRYONIC LETHALITY
UBIQUITIN LIGASE
MISMATCH REPAIR
BRCA1
MICE
IDENTIFICATION
TUMORIGENESIS
ARRY-142886
INSTABILITY
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
srep28217.pdf 1.428Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record