TRANSCRIPTIONAL AND TRANSLATIONAL DOWN-REGULATION OF H-REV107, A CLASS-II TUMOR-SUPPRESSOR GENE LOCATED ON HUMAN-CHROMOSOME 11Q11-12

The H-rev107 tumour suppressor was isolated as a gene specifically exp ressed in rat fibroblasts resistant toward malignant transformation by the activated HRAS gene (Sers et al., 1997; Hajnal et al., 1994), Her e we describe the human homologue of the rat H-rev107 gene. The predic ted rat and human proteins are highly conserved exhibiting an overall amino acid identity of 83%, The HREV107-1 gene is ubiquitously express ed 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 carcinom a, melanoma, neuroblastoma and other tumours, The H-REV107-1 protein w as not detectable in any of these tumour cells. Loss of H-REV107-1 exp ression was not restricted to cultured human tumour cell lines, but al so found in primary squamous cell carcinomas. Gross structural aberrat ions of the H-REV107-1 gene were absent in tumorigenic cell lines. Thu s, 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.