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Molecular characterisation of a panel of human ovarian carcinoma xenografts
A M Codegoni1, M I Nicoletti, G Buraggi
1Mario Negri Institute for Pharmacological Research, Milan, Italy.
Abstract:
In a panel of 16 human ovarian tumours transplanted in nude mice, the expression of genes involved in cell cycle regulation and in response to drug treatment were characterised. In the 16 tumours analysed we could not detect overexpression of Erb-B2 oncogene while expression of MDR1 mRNA was not detected in 11/15 samples and was low in 4/15 tumours. Only three tumours had mutations in the p53 gene exons 5-8 and one of these mutations did not result in any amino acid alteration. The levels of mRNA for cyclins A, D1 and E were heterogeneous with some tumours expressing high levels and others not expressing them at all. The same was found for the cyclin dependent kinases (CDK) CDK2 and CDK4 and for CDK inhibitors p21/WAF1, p27/KIP1 and p16/CDKN2. Two genes belonging to the nucleotide excision repair, ERCC1 and ERCC3 were detectable in all the samples examined, as were the genes MGMT and MAG, also involved in DNA repair. The data indicate a heterogeneity in the expression of genes considered to be involved in the cellular responses to cytotoxic drug treatment and indicate the possibility of using these tumour models to test specifically molecules with a defined mechanism of action.
Insights
This study characterized gene expression in human ovarian tumors in mice, finding significant heterogeneity in cell cycle and drug response genes. These models are suitable for testing targeted cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian tumors exhibit diverse molecular profiles.
- Understanding gene expression is crucial for targeted therapy development.
Purpose of the Study:
- To characterize gene expression related to cell cycle regulation and drug response in human ovarian tumors xenografted in nude mice.
- To assess the potential of these models for evaluating targeted therapeutic agents.
Main Methods:
- Analysis of gene expression in 16 human ovarian tumor samples xenografted in nude mice.
- Evaluation of genes involved in cell cycle regulation (cyclins, CDKs, CDK inhibitors), drug resistance (MDR1), oncogenes (Erb-B2), p53 mutations, and DNA repair (ERCC1, ERCC3, MGMT, MAG).
Main Results:
- No Erb-B2 oncogene overexpression was detected.
- MDR1 mRNA was undetectable or low in most samples.
- p53 gene mutations were infrequent.
- Heterogeneous expression of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors was observed.
- DNA repair genes (ERCC1, ERCC3, MGMT, MAG) were consistently detectable.
Conclusions:
- Human ovarian tumor xenografts display significant heterogeneity in genes associated with cellular responses to cytotoxic drugs.
- These models are valuable for testing the efficacy of drugs with specific mechanisms of action.