Protein Kinase A Regulatory Subunits in Colon Cancer

Protein Kinase A Regulatory Subunits in Colon Cancer

The protein kinase A (PKA) is classified as type I or II depending on the association of the catalytic subunit with either the RI or RII regulatory subunits. Alterations in the levels of these regulatory subunits and PKA activity itself appear to affect cellular proliferation and tumorigenesis. We e...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) Vol. 1; no. 4; pp. 373 - 378
Main Authors: Carlson, Chris C., Smithers, Stacy L., Yeh, Karen A., Burnham, Laura L., Dransfield, Daniel T.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-10-1999
Stockton Press
Elsevier
Subjects:
Adult
Aged
Aged, 80 and over
Blotting, Western
cAMP
Catalysis
catalytic subunit
Cell Division
Colonic Neoplasms - enzymology
Colonic Neoplasms - genetics
colorectal tumors
Cyclic AMP - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Electrophoresis, Polyacrylamide Gel
Female
Humans
In Vitro Techniques
Male
Middle Aged
Oligopeptides - pharmacology
Phosphorylation
protein kinase A
regulatory subunit
Signal Transduction
colorectal tumors
protein kinase A
cAMP
PKA
regulatory subunit
catalytic subunit
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Summary:The protein kinase A (PKA) is classified as type I or II depending on the association of the catalytic subunit with either the RI or RII regulatory subunits. Alterations in the levels of these regulatory subunits and PKA activity itself appear to affect cellular proliferation and tumorigenesis. We examined colorectal tumor specimens from 45 patients to investigate the potential role of cAMP-related signaling molecules in regulating tumorigenesis. Western blot analysis (PKA subunit protein levels) and in vitro kemptide phosphorylation assays (PKA catalytic subunit activity) were performed on human colorectal tumor tissue homogenates. RIα protein levels were decreased 200% in ascending and 50% in descending colonic tumors compared to adjacent mucosa. RII protein levels were decreased 77% in descending colonic tumors but no change was observed in ascending colonic tumors compared to adjacent mucosa. PKA activity and the absolute amount of catalytic subunit protein in ascending and descending tumors were unchanged compared to adjacent mucosa. Differences in cAMP-related signaling molecules exist between neoplastic and normal colorectal tissues. These differences may not only serve as potential therapeutic targets for chemotherapeutic agents, but also lead to the identification of novel regulatory mechanisms involved in cellular proliferation and tumorigenesis.
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ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1038/sj.neo.7900039