Differential Regulation of the Stability of Cyclic AMP-dependent Protein Kinase Messenger RNA in Normal versus Neoplastic Mouse Lung Epithelial Cells

Carol A. Lange-Carter, Alvin M. Malkinson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Neoplastic mouse lung epithelial cells contain greatly diminished activity, protein, and mRNA for the type I isozyme of cyclic AMPdependent protein kinase (PKA I), while expression of the type II isozyme (PKA II) is similar to that of normal lung cells. A time course of PKA mRNA content in transcriptionally inhibited cells indicated that most PKA mRNAs are more stable in the neoplastic E9 cell line than in related nontumorigenic CIO cells. To address the basis of this differential stability, we treated both cell lines with cycloheximide, an inhibitor of protein synthesis, in the presence or absence of the transcriptional inhibitor, 5,6-dichloro-l-e-ribofuranosyl-benzimidazole (DRB). The rate of PKA II regulatory subunit a mRNA decay in the presence of DRB was unaffected by cycloheximide treatment in E9 cells but decreased upon the addition of cycloheximide to DRB-treated CIO cells. The combination of these two agents markedly destabilized PKA II mRNAs (PKA catalytic subunit a and PKA II regulatory subunit a) relative to DRB treatment alone in neoplastic E9 cells, causing them to decay at a rate equal to that in CIO cells. PKA II mRNA may be specifically stabilized by a protein with a relatively short half-life in neoplastic E9 cells. These results suggest the involvement of tumor-specific factor(s) in the regulation of PKA mRNA stability, a potential mechanism for conferring the observed differential responsiveness of normal and neo plastic lung cells to cyclic AMP.

Original languageEnglish (US)
Pages (from-to)6699-6703
Number of pages5
JournalCancer Research
Volume51
Issue number24
StatePublished - Dec 1991

Fingerprint Dive into the research topics of 'Differential Regulation of the Stability of Cyclic AMP-dependent Protein Kinase Messenger RNA in Normal versus Neoplastic Mouse Lung Epithelial Cells'. Together they form a unique fingerprint.

Cite this