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Overexpression Is Associated with Resistance to Treatment with DNA-damaging Agents in a Human Ovarian Cancer Cell Line1
Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche "Mario Negri," 20157 Milan, Italy
We examined the consequences of p73
overexpression on gene expression
and cellular response to anticancer agents in clones from the human
ovarian cancer cell line A2780. Using microarray filters, the
expression of 588 genes in two clones overexpressing p73
(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, including genes
participating in nucleotide excision repair and mismatch repair. This
was confirmed by reverse transcription-PCR and Northern blot
analysis and was associated with an increase in the ability of
p73-expressing clones to repair two different DDP
(cis-dichlorodiammine platinum)-damaged plasmids in a
host reactivation assay. p73 overexpressing clones were less
sensitive than parental cells to alkylating agents treatment or UV
radiation but equally sensitive to the topoisomerase I inhibitor
topotecan, which indicated that the increase in expression of DNA
repair genes has implications for the response to DNA damaging agents.
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