作者: F R DeRubertis , R Chayoth , J B Field
DOI: 10.1172/JCI108320
关键词: Prostaglandin E 、 Intestinal mucosa 、 Biology 、 Endocrinology 、 Cyclase 、 Metabolism 、 Internal medicine 、 Theophylline 、 Adenylate kinase 、 Cyclic nucleotide 、 Cyclase 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.