Molecular characterisation of a panel of human ovarian carcinoma xenografts.
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.
Codegoni
A M
AM
Mario Negri Institute for Pharmacological Research, Milan, Italy.
Nicoletti
M I
MI
Buraggi
G
G
Valoti
G
G
Giavazzi
R
R
D'Incalci
M
M
Landoni
F
F
Maneo
A
A
Broggini
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001835:Body Weight; D002945:Cisplatin / Q000627:therapeutic use; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D019450:Genes, MDR; D018816:Genes, cdc; D018734:Genes, erbB-2 / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D051379:Mice; D009154:Mutation; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D018844:Cyclin-Dependent Kinases; D002945:Cisplatin