Laboratory of Pharmacogenetics and Molecular Toxicology, Center for Molecular and Structural Biomedicine, Institute of Biotechnology and Bioengineering, University of Algarve, Faro, Portugal.
Anticancer Res. 2013 Jun;33(6):2549-55.
We aimed to study the prevalence of Hypoxia inducible factor-1α (HIF-1α) P582S and A588T polymorphisms in a Portuguese breast cancer population and its effect on the transcriptional activity of HIF-1α in MCF7 breast adenocarcinoma cells. We performed a polymerase chain Reaction--restriction fragment length polymorphism (PCR-RFLP)-based genotyping of a Portuguese breast cancer population for two HIF-1α polymorphisms. Furthermore, by site-directed mutagenesis, we generated a variant form of HIF-1α and compared its transcriptional activity with the wild-type HIF-1α in MCF7 cells. There were no significant differences in genotypic frequencies for P582S and A588T between breast cancer patients and controls, nor between the transcriptional activity of the 582S mutant and the wild-type HIF-1α. In conclusion, there is no association between HIF-1α polymorphisms and incidence of breast cancer in the Portuguese examined population. Furthermore, the P582S mutation does not affect transcriptional activity of HIF-1α in breast cancer cells, contrary to previous findings in other cell lines, suggesting that the impact of this mutation is cell-type specific.
我们旨在研究缺氧诱导因子-1α（HIF-1α）P582S 和 A588T 多态性在葡萄牙乳腺癌人群中的流行情况及其对 MCF7 乳腺癌腺癌细胞中 HIF-1α转录活性的影响。我们对葡萄牙乳腺癌人群进行了基于聚合酶链反应-限制性片段长度多态性（PCR-RFLP）的两种 HIF-1α 多态性的基因分型。此外，通过定点诱变，我们生成了 HIF-1α 的一种变体形式，并将其转录活性与 MCF7 细胞中的野生型 HIF-1α进行了比较。在乳腺癌患者和对照组之间，P582S 和 A588T 的基因型频率没有显著差异，582S 突变体与野生型 HIF-1α 的转录活性也没有差异。总之，在本研究中检查的葡萄牙人群中，HIF-1α 多态性与乳腺癌的发生率之间没有关联。此外，与其他细胞系的先前发现相反，P582S 突变不会影响乳腺癌细胞中 HIF-1α 的转录活性，这表明该突变的影响是细胞类型特异性的。
