Akutsu N, Bastien Y, Lin R, Mader S, White J H
Department of Physiology, McGill University, Montréal, Canada.
Biochem Biophys Res Commun. 2001 Mar 9;281(4):1051-6. doi: 10.1006/bbrc.2001.4466.
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)2D3] 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)2D3 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)2D3 target gene in SCC25 cells. Induction of amphiregulin mRNA by 1,25(OH)2D3 was rapid and sustained over 48 h, and was unaffected by cycloheximide. 1,25(OH)2D3 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)2D3. Amphiregulin partially inhibited growth of SCC25 cells in culture. Our data show that amphiregulin is a 1,25(OH)2D3 target gene, and suggest that its induction may contribute to the growth inhibitory effects of 1,25(OH)2D3.
1α,25 - 二羟基维生素D(3)[1,25(OH)2D3]在体外和体内均可抑制源自多种肿瘤的细胞生长。源自舌部原发性鳞状细胞癌（SCC）的人SCC25细胞在体外的增殖受到1,25(OH)2D3及其类似物EB1089的抑制。13 - 顺式视黄酸（RA）也有类似作用，它已被用于SCC的化学预防。我们确定双调蛋白（一种表皮生长因子家族成员）是SCC25细胞中的1,25(OH)2D3靶基因。1,25(OH)2D3对双调蛋白mRNA的诱导迅速且在48小时内持续存在，并且不受放线菌酮影响。1,25(OH)2D3还可在雌激素受体阳性和阴性的人乳腺癌细胞系中诱导双调蛋白mRNA，但在LNCaP人前列腺癌细胞中则无此作用。RAR或RXR特异性类视黄醇不影响SCC25细胞中双调蛋白mRNA水平；然而，13 - 顺式RA部分阻断了对1,25(OH)2D3的反应。双调蛋白可部分抑制培养的SCC25细胞生长。我们的数据表明双调蛋白是1,25(OH)2D3的靶基因，并提示其诱导可能有助于1,25(OH)2D3的生长抑制作用。
