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Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.
Kunihisa, Tomonari; Inubushi, Sachiko; Tanino, Hirokazu; Hoffman, Robert M.
Afiliación
  • Kunihisa T; Division of Breast and Endocrine Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan.
  • Inubushi S; Division of Breast and Endocrine Surgery, Graduate School of Medicine, Kobe University, Hyogo, Japan.
  • Tanino H; Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
  • Hoffman RM; AntiCancer Inc, San Diego, CA, U.S.A.; all@anticancer.com.
Cancer Genomics Proteomics ; 21(4): 399-404, 2024.
Article en En | MEDLINE | ID: mdl-38944428
ABSTRACT
BACKGROUND/

AIM:

BRCA1/2 mutations in breast cancer cells impair homologous recombination and promote alternative end joining (Alt-EJ) for DNA-damage repair. DNA polymerase theta, encoded by POLQ, plays a crucial role in Alt-EJ, making it a potential therapeutic target, particularly in BRCA1/2-mutant cancers. Methionine restriction is a promising approach to target cancer cells due to their addiction to this amino acid. The present study investigated the expression of POLQ in BRCA1/2 wild-type and BRCA1-mutant breast cancer cells under methionine restriction. MATERIALS AND

METHODS:

POLQ mRNA expression was measured using qRT-PCR in BRCA1/2 wild-type (MDA-MB-231) and BRCA1- mutant (HCC1937 and MDA-MB-436) breast-cancer cells under normal, or serum-restricted, or serum- and methionine-restricted conditions.

RESULTS:

Compared to BRCA1/2 wild-type cells, BRCA1-mutant cells displayed significantly higher basal POLQ expression in normal medium. Methionine restriction further increased POLQ expression in the BRCA1-mutant cells but decreased it in the BRCA1/2 wild-type cells.

CONCLUSION:

The present findings suggest that methionine restriction showed differential effects on POLQ expression, potentially impacting Alt-EJ activity, in BRCA1/2 wild-type and BRCA1-mutant breast-cancer cells. Further investigation is needed to explore the potential of combining methionine restriction with DNA-repair inhibitors, such as PARP inhibitors, to overcome drug resistance in BRCA1/2 mutant cancers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteína BRCA1 / ADN Polimerasa theta / Metionina / Mutación Límite: Female / Humans Idioma: En Revista: Cancer Genomics Proteomics Asunto de la revista: BIOQUIMICA / GENETICA MEDICA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteína BRCA1 / ADN Polimerasa theta / Metionina / Mutación Límite: Female / Humans Idioma: En Revista: Cancer Genomics Proteomics Asunto de la revista: BIOQUIMICA / GENETICA MEDICA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Grecia