de Anta J M, Monzó M, Peris B, Ruano D
Department of Morphological Sciences, Faculty of Medicine, University of Barcelona, Spain.
Histol Histopathol. 1997 Jan;12(1):33-41.
The k-FGF gene, which belongs to the family of the fibroblast growth factor genes, is implicated in tumoral and developmental processes. It is expressed in embryonal carcinoma cells, in embryonic stem cells, during limb and tooth formation and in some germ cell tumors. However, the expression of this protooncogene during testicular development as well its relationship to spontaneous teratogenesis have not been determined. Here we investigate k-FGF expression during testicular development in mice, as well as in a spontaneous testicular teratoma (STT) and in the OTT6050 teratocarcinoma (TC) by Northern blotting, RT-PCR and it situ hybridization. Several data indicate that k-FGF gene contains downstream regulatory sequences which bind octamer factors. One of these transcription factors which binds to k-FGF enhancer is Oct-4. Although the k-FGF gene is activated by Oct-4 in embryonal carcinoma and embryonic stem cells and Oct-4 is expressed in the germ cells of the embryo, our results indicate that there is no detectable k-FGF expression in mouse testicular germ cells at any stage of development. This indicates that Oct-4 does not activate transcription of the k-FGF gene in mouse germ cells, and that k-FGF is not implicated during testicular development. We also show that there is a high k-FGF expression in the experimental OTT6050 TC, but only very low levels in a murine differentiated STT, suggesting that k-FGF activation may be responsible for the genesis and development of STT, behaving as a marker of malignancy in these neoplasms.
k-FGF基因属于成纤维细胞生长因子基因家族,与肿瘤发生和发育过程有关。它在胚胎癌细胞、胚胎干细胞、肢体和牙齿形成过程以及某些生殖细胞肿瘤中表达。然而,该原癌基因在睾丸发育过程中的表达及其与自发性致畸的关系尚未确定。在此,我们通过Northern印迹法、逆转录聚合酶链反应(RT-PCR)和原位杂交技术,研究k-FGF在小鼠睾丸发育过程中的表达,以及在自发性睾丸畸胎瘤(STT)和OTT6050畸胎癌(TC)中的表达。多项数据表明,k-FGF基因含有与八聚体因子结合的下游调控序列。其中一种与k-FGF增强子结合的转录因子是Oct-4。虽然k-FGF基因在胚胎癌细胞和胚胎干细胞中被Oct-4激活,且Oct-4在胚胎生殖细胞中表达,但我们的结果表明,在小鼠睾丸生殖细胞发育的任何阶段均未检测到k-FGF表达。这表明Oct-4在小鼠生殖细胞中不激活k-FGF基因的转录,且k-FGF在睾丸发育过程中不发挥作用。我们还表明,在实验性OTT6050 TC中有高k-FGF表达,但在小鼠分化型STT中表达水平极低,这表明k-FGF激活可能是STT发生和发展的原因,在这些肿瘤中可作为恶性肿瘤的标志物。