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We have shown that a mutant derivative of Chinese hamster ovary CHO-K1 cells, ADR-5, which shows hypersensitivity to topoisomerase II (topo II)-inhibitory drugs, is cross-sensitive to the site-selective cyclic AMP analogue 8-chloro-cyclic AMP. We tested the hypothesis that overexpression of the type I alpha regulatory subunit of protein kinase A may represent a common element conferring hypersensitivity to both topo II inhibitors and 8-chloro-cyclic AMP in ADR-5 cells. We have demonstrated that ADR-5 cells overexpress RI alpha protein, compared to parental CHO-K1 cells. Moreover, retroviral vector-mediated transfer of the RI alpha gene into CHO-K1 cells was able to confer a drug-hypersensitive phenotype similar to that exhibited by ADR-5 cells. Analysis of topo II protein levels and activity revealed no differences between parental and infected cells, suggesting that protein kinase A may be involved in the downstream processing of topo II-mediated events.

Type

Journal article

Journal

Cancer Res

Publication Date

01/08/1994

Volume

54

Pages

4123 - 4128

Keywords

8-Bromo Cyclic Adenosine Monophosphate, Animals, Antineoplastic Agents, Bleomycin, CHO Cells, Cell Division, Cisplatin, Cricetinae, Cyclic AMP-Dependent Protein Kinases, Drug Screening Assays, Antitumor, Etoposide, Teniposide