Abstracts
1999 Digestive Disease Week

# 2084 ALTERATIONS IN CYCLIC AMP-RELATED SIGNALING MOLECULES IN HUMAN COLORECTAL TUMOR SPECIMENS
C C Carlson, S L Simonton, K A Yeh, L L Burnham, Daniel T Dransfield, Med Coll of Georgia, Augusta, GA

The cAMP-dependent protein kinase A (PKA) is an integral part of signaling events controlling cell proliferation and tumorigenesis. The enzyme is classifed as type I or type II depending on the catalytic subunits association with either the R1 or R11 regulatory subunits. Alterations in the levels of these regulatory subunits and activity of the enzyme itself appear to affect cellular proliferation. We examined colorectal tumor specimens from 61 patients to investigate the potential role of cAMP-related signaling molecules in regulating tumorigenesis. Western blot analysis (PKA subunit protein levels), 32P-RII overlay(A-kinase anchoring protein levels), and in vitro kemptide phosphorylation (PKA activity) were performed on human colorectal tumor tissue homogenates. RIb was downregulated in right (3.5-fold), transverse (3-fold), and left (7-fold) colon tumors when compared to normal adjacent mucosa (NAM) and an apparent downregulation of RII occurred in left-sided lesions. PKA activity in right-sided and transverse tumors was increased in tumor versus NAM (2.3- and 4-fold, respectively). In patients with metastatic disease, PKA activity appeared increased in both transverse and right-sided tumors but decreased in left-sided tumors. Altered PKA activity was not due to an increase in catalytic subunit protein levels in the tumor samples. 32P-RII overlays and western blot analysis identified one AKAP (AKAP95) which was decreased (53±10%) in some tumors versus NAM. Differences in cAMP-related signaling molecules exist between neoplastic and normal colorectal tissues and may serve not only as potential therapeutic targets for chemotherapeutic agents but also may identify new regulatory mechanisms involved in cellular proliferation and tumorigenesis.

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