Kimura Tohru, Suzuki Akira, Fujita Yukiko, Yomogida Kentaro, Lomeli Hilda, Asada Noriko, Ikeuchi Megumi, Nagy Andras, Mak Tak W, Nakano Toru
Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Development. 2003 Apr;130(8):1691-700. doi: 10.1242/dev.00392.
The tumor suppressor gene PTEN, which is frequently mutated in human cancers, encodes a lipid phosphatase for phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] and antagonizes phosphatidylinositol 3 kinase. Primordial germ cells (PGCs), which are the embryonic precursors of gametes, are the source of testicular teratoma. To elucidate the intracellular signaling mechanisms that underlie germ cell differentiation and proliferation, we have generated mice with a PGC-specific deletion of the Pten gene. Male mice that lacked PTEN exhibited bilateral testicular teratoma, which resulted from impaired mitotic arrest and outgrowth of cells with immature characters. Experiments with PTEN-null PGCs in culture revealed that these cells had greater proliferative capacity and enhanced pluripotent embryonic germ (EG) cell colony formation. PTEN appears to be essential for germ cell differentiation and an important factor in testicular germ cell tumor formation.
肿瘤抑制基因PTEN在人类癌症中经常发生突变，它编码一种针对磷脂酰肌醇3,4,5-三磷酸[PtdIns(3,4,5)P3]的脂质磷酸酶，并拮抗磷脂酰肌醇3激酶。原始生殖细胞（PGC）是配子的胚胎前体，是睾丸畸胎瘤的来源。为了阐明生殖细胞分化和增殖的细胞内信号传导机制，我们构建了Pten基因在PGC中特异性缺失的小鼠。缺乏PTEN的雄性小鼠表现出双侧睾丸畸胎瘤，这是由于有丝分裂停滞受损以及具有未成熟特征的细胞过度生长所致。对培养中的PTEN缺失PGC进行的实验表明，这些细胞具有更强的增殖能力，并增强了多能胚胎生殖（EG）细胞集落的形成。PTEN似乎对生殖细胞分化至关重要，并且是睾丸生殖细胞肿瘤形成的一个重要因素。
