RT Journal Article SR Electronic T1 Properties of L-Type Amino Acid Transporter 1 in Epidermal Ovarian Cancer JF International Journal of Gynecologic Cancer JO Int J Gynecol Cancer FD BMJ Publishing Group Ltd SP 329-336 OP 329-336 DO 10.1111/IGC.0b013e3181d28e13 VO 20 IS 3 A1 Masahiko Kaji A1 Maryam Kabir-Salmani A1 Naohiko Anzai A1 Chun Ji Jin A1 Yoshihiro Akimoto A1 Ayako Horita A1 Atsuhiko Sakamoto A1 Yoshikatsu Kanai A1 Hiroyuki Sakurai A1 Mitsutoshi Iwashita YR 2010 UL http://ijgc.bmj.com/content/20/3/329-336.abstract AB Hypothesis: To investigate the expression and the functional properties of L-type amino acid transporter 1 (LAT1) in human epithelial ovarian cancer to provide a basis for potential new therapies to control the growth and the metastasis of ovarian cancer.Methods: The material used comprised 63 surgically resected specimens obtained from female patients undergoing gynecologic surgery at Kyorin University School of Medicine (Tokyo, Japan). The expression of LAT1 in 53 cases of ovarian cancers was determined by Western blot and immunohistochemical staining, and results were compared with those of normal ovarian tissues (5 cases) and benign ovarian tumors (5 cases). Furthermore, we examined the effect of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), the classic inhibitor of system L on the survival, the migration, and the uptake of l-leucine by human epithelial ovarian cancer cell line (OVCAR-3).Results: The LAT1 was significantly up-regulated in various human epithelial ovarian cancers that was localized predominantly on their plasma membrane and in the plasma membrane of the ovarian cancer cell line in conjunction with 4F2hc via disulfide bonds. The BCH inhibited the proliferation and the migration of the OVCAR-3 cells and the uptake of [14C]l-leucine by these cells in a dose-dependent manner. The OVCAR-3 cells did not express LAT2, and the uptake of [14C]l-leucine by these cells was Na+-independent and almost completely inhibited by BCH. Thus, our findings indicated that most l-leucine uptake in OVCAR-3 cells was mediated by LAT1.Conclusions: The LAT1 plays significant roles in nutrition, proliferation, and migration of ovarian cancer. Then, LAT1 inhibition would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues.