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.
CONCLUSIONS: 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.
方法:使用qRT-PCR在BRCA1/2野生型(MDA-MB-231)和BRCA1-突变型(HCC1937和MDA-MB-436)乳腺癌细胞中测量POLQmRNA的表达。或血清限制,或血清和蛋氨酸限制条件。
结果:与BRCA1/2野生型细胞相比,BRCA1突变细胞在正常培养基中表现出明显更高的基础POLQ表达。甲硫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。
结论:目前的研究结果表明,蛋氨酸限制对POLQ表达有不同的影响,可能影响Alt-EJ活动,在BRCA1/2野生型和BRCA1突变型乳腺癌细胞中。需要进一步的研究来探索结合甲硫氨酸限制和DNA修复抑制剂的潜力,如PARP抑制剂,克服BRCA1/2突变癌症的耐药性。