The content and metabolism of cyclic adenosine 3', 5'-monophosphate and cyclic guanosine 3', 5'-monophosphate in adenocarcinoma of the human colon.

作者: F R DeRubertis , R Chayoth , J B Field

DOI: 10.1172/JCI108320

关键词: Prostaglandin EIntestinal mucosaBiologyEndocrinologyCyclaseMetabolismInternal medicineTheophyllineAdenylate kinaseCyclic nucleotideCyclase activity

摘要: Abstract Data from cultured cells have suggested that cyclic AMP and GMP may be important determinants of cell growth transformation. However, few studies examined nucleotide content metabolism in naturally occurring tumors man. Accordingly, the present study we compared cAMP cGMP levels carcinomas human colon to those adjacent uninvolved mucosa after therapeutic resection these tissues. The tumors, determined samples frozen 30 min excision, was significantly lower than mucosa, when expressed on basis tissue wet weight, protein, or DNA content. By contrast, higher surrounding if calculated but this difference did not persist correction made for protein tumors. Incubation slices tumor with without theophylline vitro increased above observed same tissue. such incubations remained clearly below while two tissues differ. failure abolish differences comparable activities high low Km cAMP-phosphodiesterase homogenates a consequence diminished synthesis rather enhanced degradation. This possibility supported by reduction basal maximal prostaglandin E1 (PGE1)-responsive adenylate cyclase activity found relative incubation dose PGE1 theophylline. Since NaF-responsive reduced related deficiency catalytic unit complex role cyclase-cAMP system and/or cAMP-to-cGMP ratios pathogenesis colonic carcinoma is uncertain, changes might favor unregulated cellular proliferation.

参考文章(43)
David Rodbard, William Bridson, PL Rayford, None, RAPID CALCULATION OF RADIOIMMUNOASSAY RESULTS. Journal of Laboratory and Clinical Medicine. ,vol. 74, pp. 770- 781 ,(1969) , 10.5555/URI:PII:0022214369902388
Immanuel Schorr, P. Rathnam, B.B. Saxena, R.L. Ney, Multiple Specific Hormone Receptors in the Adenylate Cyclase of an Adrenocortical Carcinoma Journal of Biological Chemistry. ,vol. 246, pp. 5806- 5811 ,(1971) , 10.1016/S0021-9258(18)61876-9
Harold P. Morris, William L. West, Allen R. Rhoads, Cyclic 3',5'-nucleotide monophosphate phosphodiesterase activity in hepatomas of different growth rates. Cancer Research. ,vol. 32, pp. 2651- 2655 ,(1972)
Alton L. Steiner, Anthony S. Pagliara, Lewis R. Chase, David M. Kipnis, Radioimmunoassay for cyclic nucleotides. II. Adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in mammalian tissues and body fluids. Journal of Biological Chemistry. ,vol. 247, pp. 1114- 1120 ,(1972) , 10.1016/S0021-9258(19)45622-6
J Short, K Tsukada, WA Rudert, I Lieberman, Cyclic adenosine 3':5'-monophosphate and the induction of deoxyribonucleic acid synthesis in liver. Journal of Biological Chemistry. ,vol. 250, pp. 3602- 3606 ,(1975) , 10.1016/S0021-9258(19)41439-7
Wayne B. Anderson, Maria Gallo, Ira Pastan, Adenylate Cyclase Activity in Fibroblasts Transformed by Kirsten or Moloney Sarcoma Viruses Journal of Biological Chemistry. ,vol. 249, pp. 7041- 7048 ,(1974) , 10.1016/S0021-9258(19)42073-5
William H. Adler, Frederick R. DeRubertis, Thomas Hudson, Terry V. Zenser, Role of Cyclic Adenosine 3′,5′-Monophosphate in Lymphocyte Mitogenesis Journal of Immunology. ,vol. 113, pp. 151- 161 ,(1974)
ROBERT SHIELDS, Control of cell growth by the cyclic nucleotide seesaw Nature. ,vol. 252, pp. 11- 12 ,(1974) , 10.1038/252011A0
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
Charles J. Schwartz, Daniel V. Kimberg, Patricia Ware, Adenylate Cyclase in Intestinal Crypt and Villus Cells: Stimulation by Cholera Enterotoxin and Prostaglandin E1 Gastroenterology. ,vol. 68, pp. 94- 104 ,(1975) , 10.1016/S0016-5085(75)80053-9