Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.

Autor:	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.; Department of Surgery, University of California San Diego, La Jolla, CA, U.S.A.
Jazyk:	angličtina
Zdroj:	Cancer genomics & proteomics [Cancer Genomics Proteomics] 2024 Jul-Aug; Vol. 21 (4), pp. 399-404.
DOI:	10.21873/cgp.20458
Abstrakt:	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. (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze:	MEDLINE
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