乳腺癌细胞中的 BRCA1/2 突变会损害同源重组并促进用于 DNA 损伤修复的选择性末端连接 (Alt-EJ)。由 POLQ 编码的 DNA 聚合酶 theta 在 Alt-EJ 中发挥着至关重要的作用，使其成为潜在的治疗靶点，特别是在 BRCA1/2 突变癌症中。由于癌细胞对这种氨基酸的成瘾性，限制甲硫氨酸是一种很有前景的靶向癌细胞的方法。本研究调查了甲硫氨酸限制下 BRCA1/2 野生型和 BRCA1 突变型乳腺癌细胞中 POLQ 的表达。使用 qRT-PCR 测量 BRCA1/2 野生型 (MDA-MB-231) 和 BRCA1/2 野生型 (MDA-MB-231) 和BRCA1 突变体（HCC1937 和 MDA-MB-436）乳腺癌细胞在正常或血清限制或血清和蛋氨酸限制条件下。与 BRCA1/2 野生型细胞相比，BRCA1 突变细胞表现出显着更高的正常培养基中的基础 POLQ 表达。蛋氨酸限制进一步增加了 BRCA1 突变细胞中的 POLQ 表达，但降低了 BRCA1/2 野生型细胞中的 POLQ 表达。目前的研究结果表明，蛋氨酸限制对 BRCA1/2 中的 POLQ 表达表现出不同的影响，可能影响 Alt-EJ 活性野生型和 BRCA1 突变乳腺癌细胞。需要进一步研究来探索将蛋氨酸限制与 DNA 修复抑制剂（例如 PARP 抑制剂）相结合的潜力，以克服 BRCA1/2 突变癌症的耐药性。版权所有 © 2024，国际抗癌研究所（George J. Delinasios 博士） ）， 版权所有。

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.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.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.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.