Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12

Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12
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DOI:
10.1038/sj.onc.1202060
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发表时间:
1998-09-10
期刊:
影响因子:
8
通讯作者:
Schäfer, R
Schäfer, R
中科院分区:
医学1区
文献类型:
--
作者:
Husmann, K;Sers, C;Schäfer, R

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H-rev 107肿瘤抑制因子作为在大鼠成纤维细胞中特异性表达的基因被分离,所述成纤维细胞抵抗由活化的HRAS基因引起的恶性转化(Sers et al.,1997; Hajnal等人,1994),在这里,我们描述了人类同源的大鼠H-rev 107基因。预测的大鼠和人蛋白质高度保守,表现出83%的总体氨基酸同一性。HREV 107 -1基因除了造血细胞和组织之外普遍表达。相反,H-REV 107 -1 mRNA仅在来自乳腺癌、肺癌、胃癌、肾癌、黑色素瘤、神经母细胞瘤和其他肿瘤的27个细胞系中的8个中发现,H-REV 107 -1蛋白在这些肿瘤细胞中均未检测到。H-REV 107 -1表达的缺失并不局限于培养的人类肿瘤细胞系,也见于原发性鳞状细胞癌。在致瘤细胞系中不存在H-REV 107 -1基因的总体结构畸变。因此,对H-REV 107 -1表达的阻断在转录和翻译水平上实现。通过荧光原位杂交,将人H-REV 107 -1基因定位于染色体11 q11 -12。
The H-rev107 tumour suppressor was isolated as a gene specifically expressed in rat fibroblasts resistant toward malignant transformation by the activated HRAS gene (Sers et al., 1997; Hajnal et al., 1994), Here we describe the human homologue of the rat H-rev107 gene. The predicted rat and human proteins are highly conserved exhibiting an overall amino acid identity of 83%, The HREV107-1 gene is ubiquitously expressed with the exception of haematopoetic cells and tissues, In contrast, H-REV107-1 mRNA was found only in eight of 27 cell lines derived from mammary carcinoma, lung carcinoma, gastric carcinoma, kidney carcinoma, melanoma, neuroblastoma and other tumours, The H-REV107-1 protein was not detectable in any of these tumour cells. Loss of H-REV107-1 expression was not restricted to cultured human tumour cell lines, but also found in primary squamous cell carcinomas. Gross structural aberrations of the H-REV107-1 gene were absent in tumorigenic cell lines. Thus, the block to H-REV107-1 expression is achieved both at the level of transcription and translation. By fluorescence in situ hybridisation the human H-REV107-1 gene was localised to chromosome 11q11-12.