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Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, California 94121, and Departments of Medicine and Pathology, University of California School of Medicine, San Francisco, California 94143
The role of cyclic adenosine 3':5'-monophosphate (cAMP) in the regulation of the synthesis and release of glycoproteins and of carcinoembryonic antigen by colon cancer cells was studied using LS174T cells in vitro. Adenylate cyclase and cAMP phosphodiesterase activities were assessed by measuring cellular cAMP in response to forskolin and cholera toxin (adenylate cyclase activators) and to 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor). Each agent increased cAMP levels significantly. Dibutyryl-cAMP (1 mM) stimulated glycoprotein synthesis and release when [3H]fucose was used as a precursor. The synthesis and release of carcinoembryonic antigen, a membrane-associated glycoprotein antigen, was also significantly increased by these test agents. A close dose-response relationship existed for forskolin and for cholera toxin between cAMP generation and carcinoembryonic antigen release. cAMP may play a role in regulating the synthesis and release of glycoprotein antigens by colon cancer cells.
1 This study was supported by USPHS grant CA24321 from the National Cancer Institute, NIH, by the Veterans Administration Medical Research Service, and by American Cancer Society Grant PDT-293.
2 Associate Investigator of the Veterans Administration.
3 Medical Investigator of the Veterans Administration. To whom requests for reprints should be addressed.
Received 10/23/84. Revised 11/27/85. Revised 3/ 6/86. Accepted 3/26/86.
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