Disease relevance of HRASLS3

• Loss of H-REV107-1 expression was not restricted to cultured human tumour cell lines, but also found in primary squamous cell carcinomas [1].
• 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 [1].
• RT-PCR analysis and immunohistochemical investigation confirmed expression of H-REV107-1 in normal ovarian epithelial cells but down-regulation in high grade ovarian carcinomas [2].
• KRAS-transformed rat ovarian cells and PA1 teratocarcinoma cells, reversibly repress H-REV107-1 via MAP/ERK signaling [2].
• H-rev107 is downregulated in many carcinomas and tumor cell lines [3].

High impact information on HRASLS3

• Expression profiling revealed that the MAP kinase inhibitor HREV107 was expressed at a higher transcript level in resistant compared with sensitive cell lines [4].
• We analyzed H-REV107-1 in non-small cell lung carcinomas, in normal lung, and in immortalized and tumor-derived cell lines [5].
• H-REV107-1, a known member of the class II tumor suppressor gene family, is involved in the regulation of differentiation and survival [5].
• Knock-down of H-REV107-1 expression in lung carcinoma cells inhibited anchorage-dependent and anchorage-independent growth whereas overexpression of H-REV107-1 induced tumor cell proliferation [5].
• Analysis of signaling pathways potentially involved in this process demonstrated that overexpression of H-REV107-1 stimulated RAS-GTPase activity, ERK1,2 phosphorylation, and caveolin-1 expression in the cell lines analyzed [5].

Biological context of HRASLS3

• Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12 [1].
• By fluorescence in situ hybridisation the human H-REV107-1 gene was localised to chromosome 11q11-12 [1].
• By systematic analysis of a human testis library, we have isolated the hH-Rev107-3 cDNA, identical to hH-Rev107-1 cDNA, which was previously described as a class II tumor suppressor gene [6].
• A27/80 and OVCAR-3 cells overexpressing H-REV107-1 protein underwent apoptosis [2].
• These results demonstrate down-regulation of the class II tumour suppressor H-REV107-1 in human ovarian carcinomas and suggest an involvement of H-REV107-1 in interferon-dependent cell death [2].

Anatomical context of HRASLS3

• Gross structural aberrations of the H-REV107-1 gene were absent in tumorigenic cell lines [1].
• 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) [1].
• H-REV107-1 is also strongly expressed in immortalized rat and human ovarian epithelial cells in vitro, but suppressed in transformed cells by two different mechanisms [2].

References