Expression Level and Hormonal Regulation of ABC Transporters in Breast Cancer

Honorat      Mylene; Guitton      Jerome; Dumontet      Charles; Payen      Lea

doi:10.2174/1573394711107020119

Abstract

Breast cancer remains the most common malignancy amongst women and its incidence continues to increase worldwide. Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted (tamoxifen) and chemotherapeutic agents (5-FluoroUracil, methotrexate). Epidemiological observations emphasize the hormone dependency of breast cancer and the importance of endocrine therapies to treat the hormonally dependent cancers. ATP Binding Cassette (ABC) transporters form one of the largest of all protein families and are central to many important biomedical phenomena, including resistance mechanism of cancers. They are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. After providing an overview of their tissue distribution, and various procedures to experimentally quantify their transport activity, we summarized the current literature regarding the putative regulation of ABC transporter expression levels by hormonal therapies including estrogens and tamoxifen, as well as the potential impact on the overall health of patients with breast cancer. Elucidation of the resistance mechanisms in cancers is essential for the rational choice of anticancer and adjuvant therapies given to the patients.

Keywords: Breast cancer, ABC transporters, MDR phenotype, endocrine regulation, tamoxifen, epirubicin, capillary electrophoresis, chemotherapy, doxorubicine, hepatic nuclear factor, isoamylalcohol, mass spectrometry, lung resistant protein, platin, vinorelbine