[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.
Wu
Da-Long
DL
Department of Clinical Pharmacology, Affiliated Hospital, Academy of Military Medical Sciences, Beijing, PR China. dalong66@sohu.com
Huang
Feng
F
Lu
Huan-Zhang
HZ
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000502:physiology*; D019772:Topotecan / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019772:Topotecan; D008942:Mitoxantrone