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Malignant conversion of human cells by antisense cDNA to a putative tumor suppressor gene
1Center for Molecular Environmental Health, Ohio State University, Columbus 43210, USA.
Abstract:
A cell line, SCC83-01-82, derived from a human oral squamous carcinoma, was non-tumorigenic in nude mice, a characteristic of premalignant cells. Conversion of these cells to a tumorigenic phenotype with chemical mutagens did not increase mutations in hot spots or other conserved regions of p53 or H-ras genes. Investigation of the tumorigenic conversion using an expression library resulted in isolation of a previously unidentified gene, CATR1, located on the long arm of chromosome 7 at band approximately q31-32. Evidence for the involvement of this gene in conversion to tumorigenicity was demonstrated by introduction of a eukaryotic expression CATR1 construct into SCC83-01-82 cells. Transfection with the antisense construct reduced the expression of CATR1 in tumors formed by the transfected cells, suggesting that the antisense suppression of endogenous CATR1 expression appeared to be sufficient for tumorigenic conversion. These results are consistent with previous reports of cytogenetic analyses of tumors, that 7q31-32 contains a gene(s) with tumor suppressor activity; CATR1 is a candidate for this putative suppressor gene.
Insights
A novel gene, CATR1, was identified in human oral squamous carcinoma cells. Its suppression promoted tumorigenicity, suggesting CATR1 acts as a tumor suppressor gene.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- SCC83-01-82 cells, derived from human oral squamous carcinoma, are non-tumorigenic, indicating a premalignant state.
- Chemical mutagen treatment did not alter key oncogenes (p53, H-ras), suggesting alternative mechanisms for tumorigenic conversion.
Purpose of the Study:
- To identify genes involved in the conversion of premalignant oral cancer cells to a tumorigenic phenotype.
- To investigate the role of a newly identified gene, CATR1, in oral cancer development.
Main Methods:
- Utilized an expression library to screen for genes involved in tumorigenic conversion.
- Introduced a eukaryotic expression construct of CATR1 into non-tumorigenic cells.
- Employed antisense construct transfection to reduce CATR1 expression in tumors.
Main Results:
- A novel gene, CATR1, was isolated and mapped to chromosome 7q31-32.
- Introduction of CATR1 into SCC83-01-82 cells induced tumorigenicity.
- Antisense suppression of CATR1 expression reduced tumor formation, confirming its role in tumorigenesis.
Conclusions:
- CATR1 is a candidate tumor suppressor gene located at chromosome 7q31-32.
- The findings support the presence of a tumor suppressor gene in this chromosomal region.
- CATR1 plays a crucial role in the conversion of oral squamous carcinoma cells to a tumorigenic state.