Baldassarre G, Romano A, Armenante F, Rambaldi M, Paoletti I, Sandomenico C, Pepe S, Staibano S, Salvatore G, De Rosa G, Persico M G, Viglietto G
International Institute of Genetics and Biophysics, CNR, Naples, Italy.
Oncogene. 1997 Aug 18;15(8):927-36. doi: 10.1038/sj.onc.1201260.
The teratocarcinoma-derived growth factor-1 (TDGF-1) gene codes for a 188-aminoacid glycoprotein that shares structural homology with the epidermal growth factor (EGF) family of growth factors. TDGF-1 is highly expressed in the undifferentiated embryonal carcinoma stem cell line NTERA2 clone D1 (NT2/D1) and its expression is downregulated in response to differentiating agents such as retinoic acid (RA) and hexamethylen-bisacetamide (HMBA). To assess the role of TDGF-1 in the onset and/or progression of human germ cell tumors, we analysed TDGF-1 expression by Northern blot and immunostaining in a panel of 59 human germ cell tumors of different histological origins. We show that TDGF-1 expression is markedly elevated in a subset of human testicular germ cell tumors as compared to normal testes. TDGF-1 overexpression occurs in about 100% of tumors with non-seminomatous phenotype, such as embryonal carcinomas and malignant undifferentiated teratocarcinomas. To address the questions of how TDGF-1 (previously called CRIPTO) may affect the growth and/or the differentiation of embryonal carcinoma cells, we have characterized the effects of exogenous recombinant TDGF-1 protein on the proliferation rate and differentiation 'potential of NT2/D1. Exogenous TDGF-1 protein stimulated DNA synthesis and cell proliferation in both undifferentiated and differentiated NT2/D1 cells. However, TDGF-1 protein treatment was unable to block differentiation induced by both RA and HMBA. These results suggest that TDGF-1 growth factor may represent an autocrine growth factor that may be involved in the process of development of testicular neoplasms.
畸胎癌衍生生长因子-1（TDGF-1）基因编码一种由188个氨基酸组成的糖蛋白，该蛋白与表皮生长因子（EGF）家族的生长因子具有结构同源性。TDGF-1在未分化的胚胎癌细胞系NTERA2克隆D1（NT2/D1）中高度表达，其表达会因视黄酸（RA）和六甲撑双乙酰胺（HMBA）等分化剂而被下调。为了评估TDGF-1在人类生殖细胞肿瘤发生和/或进展中的作用，我们通过Northern印迹法和免疫染色分析了59例不同组织学来源的人类生殖细胞肿瘤中TDGF-1的表达情况。我们发现，与正常睾丸相比，TDGF-1在一部分人类睾丸生殖细胞肿瘤中的表达明显升高。TDGF-1的过表达发生在约100%具有非精原细胞瘤表型的肿瘤中，如胚胎癌和恶性未分化畸胎癌。为了解决TDGF-1（以前称为CRIPTO）如何影响胚胎癌细胞的生长和/或分化的问题，我们已经研究了外源性重组TDGF-1蛋白对NT2/D1细胞增殖率和分化潜能的影响。外源性TDGF-1蛋白在未分化和分化的NT2/D1细胞中均刺激了DNA合成和细胞增殖。然而，TDGF-1蛋白处理无法阻断由RA和HMBA诱导的分化。这些结果表明，TDGF-1生长因子可能代表一种自分泌生长因子，可能参与睾丸肿瘤的发生过程。
