p73 alpha overexpression is associated with resistance to treatment with DNA-damaging agents in a human ovarian cancer cell line

We examined the consequences of p73 alpha overexpression on gene expression and cellular response to anticancer agents in clones from the human ovaria n cancer cell line A2780, Using microarray filters, the expression of 588 g enes in two clones overexpressing p73 alpha (A2780/p73.4 and A2780/ p73.5) in comparison with empty vector-transfected cells was evaluated. There were clear differences in gene expression profiles. Both of the clones showed a marked increase in the expression of genes involved in DNA repair, includi ng genes participating in nucleotide excision repair and mismatch repair. T his was confirmed by reverse transcription-PCR and Northern blot analysis a nd was associated with an increase in the ability of p73 alpha -expressing clones to repair two different DDP (cis-dichlorodiammine platinum)-damaged plasmids in a host reactivation assay. p73 alpha overexpressing clones were less sensitive than parental tells to alkylating agents treatment or UV ra diation but equally sensitive to the topoisomerase I inhibitor topotecan, w hich indicated that the increase in expression of DNA repair genes has impl ications For the response to DNA damaging agents.