BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine.
Sci Rep
; 6: 28217, 2016 06 17.
Article
en En
| MEDLINE
| ID: mdl-27313062
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tioguanina
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Neoplasias de la Mama
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Proteína BRCA1
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MAP Quinasa Quinasa 1
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MAP Quinasa Quinasa 2
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Inhibidores de Proteínas Quinasas
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Antimetabolitos Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Límite:
Female
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Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article