Amphiregulin is a vitamin D3 target gene in squamous cell and breast carcinoma

1 alpha ,25-Dihydroxyvitamin D-3 [1,25(OH)(2)D-3] inhibits growth of cells derived from a variety of tumors in vitro and in vivo. Proliferation in vitro of human SCC25 cells, derived from a primary squamous cell carcinoma (SCC) of the tongue, was blocked by 1,25(OH)(2)D-3 and its analog EB1089. A similar effect was observed with 13-cis retinoic acid (RA), which has been used in chemoprevention of SCC. We identified amphiregulin, a member of the epidermal growth factor family, as a 1,25(OH)(2)D-3 target gene in SCC25 cells. Induction of amphiregulin mRNA by 1,25(OH)(2)D-3 was rapid and sustained over 48 h, and was unaffected by cycloheximide. 1,25(OH)(2)D-3 also induced amphiregulin mRNA in estrogen receptor-positive and -negative human breast cancer cell lines, but not in LNCaP human prostate cancer cells. RAR- or RXR-specific retinoids did not affect amphiregulin mRNA levels in SCC25 cells; however, 13-cis RA partially blocked the response to 1,25(OH)(2)D-3. Amphiregulin partially inhibited growth of SCC25 cells in culture. Our data show that amphiregulin is a 1,25(OH)(2)D-3 target gene, and suggest that its induction may contribute to the growth inhibitory effects of 1,25(OH)(2)D-3. (C) 2001 Academic Press.