Myers R L, Chedid M, Tronick S R, Chiu I M
Department of Internal Medicine, Ohio State University, Columbus 43210, USA.
Oncogene. 1995 Aug 17;11(4):785-9.
We have previously reported the tissue specific distribution of four different FGF-1 transcripts containing alternative 5' untranslated exons spliced to the first protein coding exon. The predominant transcript in brain is FGF-1.B and in kidney FGF-1.A. Others have shown, by in situ hybridization and immunohistochemical analysis, that expression of FGF-1 in the brain is exclusively in neural cells but not in glial cells. Here we have examined the distribution of FGF-1.B and FGF-1.A transcripts in glioblastoma and retinal tissues and in kidney carcinoma cell lines. Our results show that FGF-1.B is the predominant transcript in neural derived tissues including both the diabetic retina and normal retina tissues. Surprisingly, FGF-1.B transcript is highly expressed in glioblastoma tissues. In contrast, a normal brain glial cell line, CHII, expresses very low levels of FGF-1 mRNA. These results strongly implicate the role of FGF-1 in the etiology of glioblastoma. We also examined several kidney carcinoma derived cell lines for the expression of FGF-1 mRNA. Most of these kidney cell lines do not express any FGF-1 transcripts. An interpretation by deduction is that kidney adenocarcinomas are derived from cortex but medulla has been reported as the site of FGF-1 synthesis. Of the kidney derived cell lines which are positive for FGF-1 message, only one expressed FGF-1.A transcript. The data may suggest that the establishment of kidney cell lines results in a switch of promoter usage from the 1.A seen in kidney tissue. Similarly, culturing of glioma cell lines may result in a switch from FGF-1.B seen in glioma tissues to FGF-1.D seen in most glioma cell lines. Continued studies of the FGF-1 transcripts, their functional promoters and their tissues distribution will provide insight into the potential role of FGF-1 in cell growth, tissue differentiation and malignant transformation.
我们之前报道过四种不同的FGF-1转录本的组织特异性分布,这些转录本包含与第一个蛋白质编码外显子剪接的可变5'非翻译外显子。大脑中主要的转录本是FGF-1.B,肾脏中是FGF-1.A。其他人通过原位杂交和免疫组化分析表明,FGF-1在大脑中的表达仅存在于神经细胞而非胶质细胞中。在此,我们检测了FGF-1.B和FGF-1.A转录本在胶质母细胞瘤、视网膜组织以及肾癌细胞系中的分布。我们的结果显示,FGF-1.B是神经源性组织中的主要转录本,包括糖尿病视网膜和正常视网膜组织。令人惊讶的是,FGF-1.B转录本在胶质母细胞瘤组织中高表达。相比之下,一种正常的脑胶质细胞系CHII表达的FGF-1 mRNA水平非常低。这些结果强烈暗示了FGF-1在胶质母细胞瘤病因学中的作用。我们还检测了几种肾癌细胞系中FGF-1 mRNA的表达。这些肾细胞系中的大多数不表达任何FGF-1转录本。通过推理得出的一种解释是,肾腺癌起源于皮质,但据报道髓质是FGF-1合成的部位。在FGF-1信息呈阳性的肾源性细胞系中,只有一个表达FGF-1.A转录本。这些数据可能表明,肾细胞系的建立导致启动子使用从肾脏组织中所见的1.A发生了转变。同样,胶质瘤细胞系的培养可能导致从胶质瘤组织中所见的FGF-1.B转变为大多数胶质瘤细胞系中所见的FGF-1.D。对FGF-1转录本、其功能性启动子及其组织分布的持续研究将为深入了解FGF-1在细胞生长、组织分化和恶性转化中的潜在作用提供线索。