Dutertre M, Rey R, Porteu A, Josso N, Picard J Y
Unité de Recherches sur l'Endocrinologie du Développement (INSERM), Ecole Normale Supérieure, Département de Biologie, Montrouge, France.
Mol Cell Endocrinol. 1997 Dec 31;136(1):57-65. doi: 10.1016/s0303-7207(97)00214-1.
Anti-Müllerian hormone (AMH) induces the regression of Müllerian ducts in the male foetus; it is secreted by prepubertal testicular Sertoli cells and repressed at puberty. Using an AMH promoter/Simian virus 40 (SV40) oncogene fusion gene, we generated transgenic mouse lines exhibiting heritable Sertoli cell tumorigenesis. One cell line, derived from an adult male, expressed mRNAs characteristic of mature Sertoli cells, but no AMH. Two other cell lines were obtained from pretumoral testes at 6.5 days. One was cloned to yield SMAT1, whose expression pattern was characteristic of prepubertal Sertoli cells, namely no transferrin and high SF-I and AMH expression. SMAT1 also secretes AMH protein into the culture medium and expresses the AMH receptor. To the best of our knowledge, this is the first Sertoli cell line stably expressing AMH and its receptor. Our results show that, in targeted oncogenesis, the timing of cell line derivation plays a critical role even when using a developmentally regulated promoter.
抗苗勒管激素(AMH)可诱导雄性胎儿苗勒管退化;它由青春期前睾丸支持细胞分泌,在青春期受到抑制。利用AMH启动子/猴病毒40(SV40)癌基因融合基因,我们构建了表现出遗传性支持细胞瘤变的转基因小鼠品系。一个源自成年雄性的细胞系表达成熟支持细胞特有的mRNA,但不表达AMH。另外两个细胞系是从6.5天时的肿瘤前睾丸中获得的。其中一个被克隆得到SMAT1,其表达模式是青春期前支持细胞特有的,即不表达转铁蛋白,而SF-I和AMH表达较高。SMAT1还将AMH蛋白分泌到培养基中并表达AMH受体。据我们所知,这是第一个稳定表达AMH及其受体的支持细胞系。我们的结果表明,在靶向肿瘤发生中,即使使用发育调控的启动子,细胞系衍生的时间也起着关键作用。