strogens enhance proliferation of estrogen receptor positive (ER+) breast cancer cells, a process requiring a high supply of amino acids (Bhat & Vadgama, 2002). System A amino acid transport activity is expressed in abundance in tissues undergoing rapid growth and proliferation (e.g. tumor cells) and it has been suggested that increased proliferation and invasiveness of neoplastic cells is linked to changes in System A function (Singh et al 1996). Three isoforms of System A (SNAT1,2,4) have been identified, which have distinct substrate specificity and tissue expression patterns (Mackenzie & Erickson, 2004 for review). The aims of this study are to establish (i) which SNAT transporter isoforms are expressed in human breast cancer cells, (ii) whether System A is estrogen-sensitive in ER+ cells and (iii) whether suppressing activity of System A reduces growth and proliferation of tumor cells in culture. The MCF-7 (ER+) breast tumor cell line was cultured in Dulbecco′s Modified Eagles Medium containing 10% fetal bovine serum. Na+-dependent uptake of [¹⁴C]Me-AIB (methylaminoisobutyric acid, a selective System A substrate) was used as a functional assay of System A activity. Cell proliferation was assessed by monitoring total cell number using a Coulter counter.SNAT1 and 2 (but not SNAT4) mRNAs were detected in MCF-7 cells by RT-PCR. System A transport activity is upregulated by estrogen (10nM 17 β-estradiol) in MCF-7 cells (48% increase in V_max from 16.6 ± 0.3 nmol. mg protein^-1. 20 min^-1 after 48h). K_m for MeAIB remained unchanged at 1.0 ± 0.1 mM, consistent with the up-regulation of SNAT2. Furthermore, blockade of System A transport using the nonmetabolisable competitive substrate MeAIB prevents the accelerated cellular proliferation otherwise induced by estrogen treatment (see Figure 1). The results show that upregulation of System A transport activity by 17β-Estradiol in MCF-7 breast cancer cells is associated with enhanced cellular proliferation and also that blocking this transport activity arrests the proliferative effect of the hormone. These observations raise the possibility of targeting System A in therapies for breast tumors.