MCF-7 Breast Cancer Cell Line, a Model for the Study of the Association Between Inflammation and ABCG2-Mediated Multi Drug Resistance

Abstract

Breast cancer is one of the most common and serious malignancies worldwide. Despite intensive cancer control efforts, it remains the second-leading cause of cancer death among women (Harris et al., 2000). While the overall response rate can be high, the duration of response is relatively short, and most patients with initially responsive tumors will experience a drug-resistance phenotype. Therefore, a lot of studies have centered on the field of drug resistance to improve cancer chemotherapy and management of cancers Gottesman, 2002). The development of intrinsic or acquired resistance to a wide variety of anticancer drugs is a major obstacle to successful cancer chemotherapy. Some cancers show primary resistance or natural resistance in which they do not respond to standard chemotherapy drugs from the beginning. On the other hand, many types of sensitive tumors respond well to chemotherapy drugs in the beginning but show acquired resistance later (Choi, 2005). Multidrug resistance (MDR) can be defined as the intrinsic or acquired resistance of cancer cells to multiple classes of structurally and mechanistically unrelated antitumor drugs (Teodori et al., 2002). To date, the most widely studied cellular mechanisms of MDR are those associated with drug efflux involving members of the adenosine triphosohate-binding cassette (ABC) membrane transporter family (Mao et al., 2005). Recently, several human ABC transporters with a potential role in drug resistance have been discovered. Among them, a novel known protein is ATP-binding cassette sub-family G member 2 (ABCG2). Human ABCG2 (also known as MXR, BCRP, and ABCP) was first cloned by Doyle et al. (Doyle et al., 1998) in the drug-resistant breast cancer cell line (MCF-7). ABCG2 is an efflux pump, which transports a variety of xenobiotics and endogenous compounds across cellular membranes. Tissue localization of ABCG2 in the mammary glands, intestine, kidney, liver, ovary, testis, placenta, endothelium and in hematopoietic stem cells indicates that ABCG2 plays an important role in absorption, distribution, and elimination of its substrates (Krishnamurthy et al., 2004; Mao & Unadkat, 2005). The expression of ABCG2 protein and/or mRNA has been detected in numerous types of human cancers (Diestra et al., 2002; Ross et al., 2000), and a large spectrum of anticancer drugs are effluxed by ABCG2