乳腺癌耐药蛋白--肿瘤多药耐药研究新进展

乳腺癌耐药蛋白（breast cancer resistance protein,BCRP)是近年发现的与肿瘤多药耐药有关的新的药物排出泵。BCRP是含655个氨基酸残基的跨膜蛋白,属于ABC转运蛋白超家族的成员,BCRP仅有6个跨膜区和1个ATP的结合位点,故被称为不完整转运分子,推测BCRP通过组成同二聚体或异二聚体构成跨膜通道而发挥功能,过表达BCRP的肿瘤细胞株对米托蒽醌,阿霉素,柔红霉素,鬼臼乙叉甙,拓扑替康,CPT－11等产生交叉耐药,而对长春新碱,紫杉醇无交叉耐药,GF120918和Fumitremorgin C能有效逆转过表达BCRP的肿瘤细胞株的耐药性,并与细胞内药物蓄积量呈正相关,人体正常组织中胎盘合体滋养层细胞,小肠和结肠粘膜上皮细胞,胆小管膜,乳腺小叶及血管内皮细胞和干细胞均能检测到BCRP的表达,推测BCRP具有抑制消化道吸收某些外源性物质（包括抗癌药和有毒物质）,参与形成胎盘屏障等生理功能,BCRP与急性髓性白血病,非小细胞肺癌,乳腺癌等多种肿瘤的临床化疗敏感性有关。

Drug-resistant proteins in breast cancer: recent progress in multidrug resistance

Breast cancer resistance protein (BCRP) is a new multidrug resistance related transmembrane transporter. BCRP is a 655 amino acid, 72 6 kDa protein, localized in the plasma membrane. As a member of the ATP binding cassette family of drug transporters, BCRP has only one ATP binding cassette and six putative transmembrane domains, suggesting that BCRP is a half transporter, which may function as a homodimer or heterodimer. The BCRP overexpressing tumor cells are resistant to mitoxantrone, adriamycin, daunorubicin, etoposide, topotecan and irinotecan, but lack resistance to paclitaxel and vincristine. Fumitremorgin C and GF120918 can effectively reverse multidrug resistance in BCRP overexpressing tumor cells, associated with an increase in drug accumulation. In normal human tissues, low to high expressions of BCRP in placental syncytiotrophoblasts, in the epithelium of the small intestine and colon, in the liver canalicular membrane, in ducts of the breast, in endothelium of the blood vessel and in stem cells were reported. This expression profile allows speculation on a role of BCRP in protection of the fetus and in the regulation of transport of chemicals through the epithelium of the gastrointestinal tract. BCRP can account for chemoresistance of some clinical cancers such as acute myeloid leukemia, non small cell lung cancer,and breast cancer.