Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diglycerides (DGs) have been found in fecal extracts at concentrations which induce mitogenesis of adenoma and some carcinoma cells but not normal cells in primary culture. DGs containing stearic, oleic, palmitic, and myristic acid side chains were found in fecal extracts from each of eight subjects. Synthetic 1,2-DGs, containing the fatty acids found in endogenous fecal DGs, induced mitogenesis in cultures of premalignant cells from each of 13 adenomas, covering all histological classes, and in cultures from two of four carcinomas. The potent adenoma mitogen, dimyristin, had no mitogenic activity on cultures of normal colonic epithelial cells from seven different subjects. These results suggest DGs may act as endogenous mitogens in the development of human colon cancer. The extent of adenoma mitogenesis was correlated with the chain length of the saturated R-groups: 16 greater than 14 greater than 12 greater than 10 greater than 8 much greater than 18. DGs with oleic acid residues, C18:1, were among the most active, while substitution of even one fatty acid residue with a stearic acid residue, C18:0, reduced or eliminated mitogenic activity. Dimyristin also induced enhanced levels of urokinase secretion from carcinoma cells, in parallel to the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. These results imply that DGs found in the colon induce a selective growth of benign colonic tumors and some carcinomas, and may enhance the invasive capacity of carcinomas, while leaving normal cells unaffected.
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PMID:Fecal diglycerides as selective endogenous mitogens for premalignant and malignant human colonic epithelial cells. 291 Apr 75

Evidence from use of pertussis and cholera toxins and from NaF suggested the involvement of G proteins in GnRH regulation of gonadotrope function. We have used three different methods to assess GnRH receptor regulation of G(q/11)alpha subunits (G(q/11)alpha). First, we used GnRH-stimulated palmitoylation of G(q/11)alpha to identify their involvement in GnRH receptor-mediated signal transduction. Dispersed rat pituitary cell cultures were labeled with [9,10-(3)H(N)]-palmitic acid and immunoprecipitated with rabbit polyclonal antiserum made against the C-terminal sequence of G(q/11)alpha. The immunoprecipitates were resolved by 10% SDS-PAGE and quantified. Treatment with GnRH resulted in time-dependent (0-120 min) labeling of G(q/11)alpha. GnRH (10(-12), 10(-10), 10(-8), or 10(-6) g/ml) for 40 min resulted in dose-dependent labeling of G(q/11)alpha compared with controls. Cholera toxin (5 microg/ml; activator of G(i)alpha), pertussis toxin (100 ng/ml; inhibitor of G(i)alpha actions) and Antide (50 nM; GnRH antagonist) did not stimulate palmitoylation of G(q/11)alpha above basal levels. However, phorbol myristic acid (100 ng/ml; protein kinase C activator) stimulated the palmitoylation of G(q/11)alpha above basal levels, but not to the same extent as 10(-6) g/ml GnRH. Second, we used the ability of the third intracellular loop (3i) of other seven-transmembrane segment receptors that couple to specific G proteins to antagonize GnRH receptor-stimulated signal transduction and therefore act as an intracellular inhibitor. Because the third intracellular loop of alpha1B-adrenergic receptor (alpha1B 3i) couples to G(q/11)alpha, it can inhibit G(q/11)alpha-mediated stimulation of inositol phosphate (IP) turnover by interfering with receptor coupling to G(q/11)alpha. Transfection (efficiency 5-7%) with alpha1B 3i cDNA, but not the third intracellular loop of M1-acetylcholine receptor (which also couples to G(q/11)alpha), resulted in 10-12% inhibition of maximal GnRH-evoked IP turnover, as compared with vector-transfected GnRH-stimulated IP turnover. The third intracellular loop of alpha2A adrenergic receptor, M2-acetylcholine receptor (both couple to G(i)alpha), and D1A-receptor (couples to G(s)alpha) did not inhibit IP turnover significantly compared with control values. GnRH-stimulated LH release was not affected by the expression of these peptides. Third, we assessed GnRH receptor regulation of G(q/11)alpha in a PRL-secreting adenoma cell line (GGH(3)1') expressing the GnRH receptor. Stimulation of GGH(3)1' cells with 0.1 microg/ml Buserelin (a metabolically stable GnRH agonist) resulted in a 15-20% decrease in total G(q/11)alpha at 24 h following agonist treatment compared with control levels; this action of the agonist was blocked by GnRH antagonist, Antide (10(-6) g/ml). Neither Antide (10(-6) g/ml, 24 h) alone nor phorbol myristic acid (0.33-100 ng/ml, 24 h) mimicked the action of GnRH agonist on the loss of G(q/11)alpha immunoreactivity. The loss of G(q/11)alpha immunoreactivity was not due to an effect of Buserelin on cell-doubling times. These studies provide the first direct evidence for regulation of G(q/11)alpha by the GnRH receptor in primary pituitary cultures and in GGH3 cells.
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PMID:Regulation of G(q/11)alpha by the gonadotropin-releasing hormone receptor. 917 Dec 37