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Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization
M J Stassar1, G Devitt, M Brosius
1Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, 69120.
Abstract:
Renal cell carcinoma (RCC) are frequently chemo- and radiation resistant. Thus, there is a need for identifying biological features of these cells that could serve as alternative therapeutic targets. We performed suppression subtractive hybridization (SSH) on patient-matched normal renal and RCC tissue to identify variably regulated genes. 11 genes were strongly up-regulated or selectively expressed in more than one RCC tissue or cell line. Screening of filters containing cancer-related cDNAs confirmed overexpression of 3 of these genes and 3 additional genes were identified. These 14 differentially expressed genes, only 6 of which have previously been associated with RCC, are related to tumour growth/survival (EGFR, cyclin D1, insulin-like growth factor-binding protein-1 and a MLRQ sub-unit homologue of the NADH:ubiquinone oxidoreductase complex), angiogenesis (vascular endothelial growth factor, endothelial PAS domain protein-1, ceruloplasmin, angiopoietin-related protein 2) and cell adhesion/motility (protocadherin 2, cadherin 6, autotaxin, vimentin, lysyl oxidase and semaphorin G). Since some of these genes were overexpressed in 80-90% of RCC tissues, it is important to evaluate their suitability as therapeutic targets.
Insights
Researchers identified 14 genes differentially expressed in renal cell carcinoma (RCC) tissues, offering potential new therapeutic targets for this chemo- and radiation-resistant cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Renal cell carcinoma (RCC) exhibits resistance to conventional chemotherapy and radiation.
- Identifying novel therapeutic targets is crucial for improving RCC treatment outcomes.
Purpose of the Study:
- To identify genes with differential expression in RCC compared to normal renal tissue.
- To discover potential new therapeutic targets for renal cell carcinoma.
Main Methods:
- Suppression subtractive hybridization (SSH) was employed to compare gene expression between patient-matched normal renal and RCC tissues.
- Differential gene expression was validated through screening of cancer-related cDNA filters and confirmed for specific genes.
Main Results:
- 14 differentially expressed genes were identified in RCC tissues and cell lines.
- These genes are implicated in tumor growth/survival, angiogenesis, and cell adhesion/motility.
- Six of the identified genes have no prior association with RCC, highlighting novel findings.
Conclusions:
- Several identified genes, including EGFR, vascular endothelial growth factor, and vimentin, are significantly overexpressed in a high percentage of RCC tissues.
- These overexpressed genes represent promising candidates for further investigation as potential therapeutic targets for renal cell carcinoma.