CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cvijic, M. E.
Right arrow Articles by Chin, K. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cvijic, M. E.
Right arrow Articles by Chin, K. V.

Cell Growth & Differentiation, Vol 8, Issue 12 1243-1247, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Regulation of P-glycoprotein expression in cyclic AMP-dependent protein kinase mutants

ME Cvijic and KV Chin
Department of Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick 08901, USA.

Multidrug resistance (MDR) in cancer poses a major obstacle to the success of chemotherapy. We previously reported that cyclic AMP (cAMP)-resistant mutants of the Chinese hamster ovary and the mouse adrenal cortical carcinoma cells harboring defective regulatory (RI alpha) subunits of the cAMP-dependent protein kinase (PKA) are more sensitive than wild-type cells to chemotherapeutic agents that are substrates for P-glycoprotein. In addition, a transfectant overexpressing a mutant RI alpha cDNA showed similar increased sensitivity to these drugs. The altered drug sensitivity in the RI alpha mutants results from reduced expression of the mdr gene, suggesting that PKA may regulate its expression. In this study, we evaluated the sensitivity of several Chinese hamster ovary catalytic (C) subunit mutants to various anticancer drugs. Like the RI alpha subunit mutant, the C subunit mutants also exhibit decreased kinase activity and unresponsiveness to growth inhibition by cAMP. However, in contrast to the RI alpha subunit mutant, the C subunit mutants are not multidrug sensitive and maintain P-glycoprotein expression levels comparable to those of wild-type cells. Furthermore, the C subunit mutants display the same resistance patterns as wild-type cells to P-glycoprotein substrates, including Adriamycin, Taxol, and colchicine. No significant difference was observed in their sensitivity to non-MDR drugs, such as 5-fluorodeoxyuridine, between wild-type, RI alpha, and C subunit mutant cells. These results suggest that the increased multidrug sensitivity in the PKA mutant cells results from alteration of the RI alpha subunit and not the kinase activity, thus implying novel functions for the RI alpha subunit. Therefore, genetic alteration of the RI alpha subunit of PKA may modulate drug resistance in cancer.


This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
M. E. Cvijic, T. Kita, W. Shih, R. S. DiPaola, and K.-V. Chin
Extracellular Catalytic Subunit Activity of the cAMP-dependent Protein Kinase in Prostate Cancer
Clin. Cancer Res., June 1, 2000; 6(6): 2309 - 2317.
[Abstract] [Full Text]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.