Taheri M, Mahjoubi F, Omranipour R
Departament of Clinical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Genet Mol Res. 2010 Jan 12;9(1):34-40. doi: 10.4238/vol9-1gmr669.
One of the limitations in the treatment of cancer patients with chemotherapy is the development of multidrug resistance (MDR). A well-known mechanism responsible for drug resistance is over-expression of ABC-transporter genes such as MDR1. This gene encodes p-glycoprotein (P-gp), a transmembrane glycoprotein that transports many hydrophobic substrates and anti-cancer drugs out of the cell. MDR1 gene polymorphisms could alter the expression level of P-gp and consequently result in drug resistance. We investigated a possible association between MDR1 gene C3435T polymorphism and its expression in Iranian breast cancer patients. PCR-RFLP was used for the detection of C3435T single nucleotide polymorphism in 54 breast cancer patients and 50 healthy individuals. The expression level of MDR1 was determined by real-time quantitative PCR. We observed no difference in the frequency of C3435T polymorphism between breast cancer patients and healthy controls. However, there was a significant association between MDR1 expression levels and C3435T polymorphism in the patients. C3435T polymorphism may play a role in inducing drug resistance by altering the expression level of the MDR1 gene.
用化疗治疗癌症患者的局限性之一是多药耐药性（MDR）的产生。一种众所周知的耐药机制是ABC转运蛋白基因如MDR1的过度表达。该基因编码P-糖蛋白（P-gp），一种跨膜糖蛋白，可将许多疏水性底物和抗癌药物转运出细胞。MDR1基因多态性可能会改变P-gp的表达水平，从而导致耐药性。我们研究了伊朗乳腺癌患者中MDR1基因C3435T多态性与其表达之间的可能关联。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测54例乳腺癌患者和50例健康个体的C3435T单核苷酸多态性。通过实时定量聚合酶链反应测定MDR1的表达水平。我们观察到乳腺癌患者和健康对照之间C3435T多态性的频率没有差异。然而，患者中MDR1表达水平与C3435T多态性之间存在显著关联。C3435T多态性可能通过改变MDR1基因的表达水平在诱导耐药性中发挥作用。
