The purpose of this study is to investigate the differential expression and function of Organic Anion Transporting Polypeptides (OATPs) in breast epithelial and breast cancer cells. E3S, a substrate for seven out of eleven OATPs, is a predominant source of tumor estrogen in post menopausal hormone dependent breast cancer patients. Over expression of certain OATPs (e.g. OATP1A2) reported in breast tumour tissues compared to surrounding normal tissues, could contribute towards 2-3 times higher tumoral E3S concentration. Little is known about the expression and function of other OATP family members among breast epithelial and breast cancer cells. We therefore compared gene and protein expression of seven OATPs (i.e. OATP1A2, OATP1B1, OATP1B3, OATP1C1, OATP2B1, OATP3A1 and OATP4A1) in normal breast epithelial cells (MCF10A), hormone dependent (MCF7) and hormone independent breast cancer cells (MDA/LCC6-435, MDA-MB-231, MDA-MB-468) by qPCR and immunoblotting. Expression of SLCO1A2, 1B1, 1B3, 2B1 and 3A1 is exclusive, similar or significantly higher in cancer cells compared to MCF10A. Protein expression of OATPs is found to be either exclusive or higher in cancer cells compared to MCF10A. Specificity of OATP mediated E3S uptake is only observed in cancer cells, with highest total uptake in MCF7 cells. Transport kinetics of E3S uptake demonstrate transport efficiency to be 10 times greater in the MCF7 cells than in the hormone independent cells. These data suggest that OATPs could be a novel therapeutic target for hormone dependent breast cancers, particularly in post menopausal patients, where the major source of tumour estrogen is E3S.
- Received January 23, 2012.
- Revision received April 24, 2012.
- Accepted May 14, 2012.
- The American Society for Pharmacology and Experimental Therapeutics