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 Iα 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 RIα protein, compared to parental CHO-K1 cells. Moreover, retroviral vector-mediated transfer of the RIα 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.

Overexpression of the RIα subunit of Protein Kinase A confers hypersensitivity to topoisomerase II inhibitors and 8-Chloro-cyclic Adenosine 3′,5′-Monophosphate in chinese hamster ovary cells.

PEPE, Stefano;
1994-01-01

Abstract

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 Iα 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 RIα protein, compared to parental CHO-K1 cells. Moreover, retroviral vector-mediated transfer of the RIα 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3881560
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