Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stable coexpression of the human retinoblastoma protein (pRB) cDNA and EJ c-Ha-ras oncogene in murine fibroblasts leads to loss of pRB expression with concomitant transformation of the cells (1). We show here that conditional expression of p21ras in mouse fibroblasts expressing human pRB leads to a rapid decrease of pRB expression at both protein and mRNA levels. The decrease of pRB mRNA is blocked by cycloheximide, suggesting the requirement of ongoing protein synthesis. p21ras expression leads also to decreases of c-myc and tissue metalloproteinase inhibitor-2 mRNAs, whereas cyclin-dependent kinase 4, cyclin D1, E2F-1, and ornithine decarboxylase are unaffected. The decrease in pRB is accompanied by progressive morphological transformation of the cells. The effect of p21ras on pRB expression was serum and growth factor dependent. A shift of the cells to low serum (0.2% FCS) abolished the effects of p21ras on pRB, but this effect was reconstituted by the addition of growth factors epidermal growth factor, fibroblast growth factor-2, transforming growth factor beta 1, and platelet-derived growth factor to the cells. The results suggest a complex interaction between p21ras, pRB, and growth factors in the control of cell growth. p21ras appears to drive the cell cycle by deregulation of key cell cycle regulators, the functions of which in low serum become redundant or require the presence of growth factors positively driving the cell cycle.
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PMID:p21ras-mediated decrease of the retinoblastoma protein in fibroblasts occurs through growth factor-dependent mechanisms. 895 39

By crossing TG.AC v-Ha-ras and K6/ODC transgenic mice, we found previously that an activated ras and follicular ornithine decarboxylase (ODC) overexpression cooperate to generate spontaneous tumors in the skin. Cellular proliferation was dramatically increased in the K6/ODC transgenic skin, as evidenced by elevated proliferating cell nuclear antigen and Ki67 expression compared with nontransgenic littermates. Keratinocytes isolated from transgenic skin also displayed increased clonal growth. Paradoxically, expression of the growth inhibition-associated proteins p53, p21Waf1, p27Klp1, and Bax was increased with ODC overexpression in the skin. ODC overexpression did not affect cyclin D/cyclin-dependent kinase 4 (Cdk4)-dependent phosphorylation of retinoblastoma protein but stimulated cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity, with minimal effect on the levels of these proteins. Thus, ODC/polyamine-induced activation of cyclin E/Cdk2 and cyclin A/Cdk2-associated kinase activity may cooperate with the ras induction of cyclin D/Cdk4/6-associated retinoblastoma protein phosphorylation to not only stimulate proliferation but ultimately contribute to tumor development.
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PMID:Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin. 1059 50

Dietary oxidants like lipid hydroperoxides (LOOH) can perturb cellular glutathione/glutathione disulphide (GSH/GSSG) status and disrupt mucosal turnover. This study examines the effect of LOOH on GSH/GSSG balance and phase transitions in the human colon cancer CaCo-2 cell. LOOH at 1 or 5 micro m were noncytotoxic, but disrupted cellular GSH/GSSG and stimulated proliferative activity at 6 h that paralleled increases in ornithine decarboxylase activity, thymidine incorporation, expression of cyclin D1/cyclin-dependent kinase 4, phosphorylation of retinoblastoma protein, and cell progression from G0/G1 to S. At 24 h, LOOH-induced sustained GSH/GSSG imbalance mediated growth arrest at G0/G1 that correlated with suppression of proliferative activity and enhanced oxidative DNA damage. LOOH-induced cell transitions were effectively blocked by N-acetylcysteine. Collectively, the study shows that subtoxic LOOH levels induce CaCo-2 GSH/GSSG imbalance that elicits time-dependent cell proliferation followed by growth arrest. These results provide insights into the mechanism of hydroperoxide-induced disruption of mucosal turnover with implications for understanding oxidant-mediated genesis of gut pathology.
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PMID:Lipid peroxide-induced redox imbalance differentially mediates CaCo-2 cell proliferation and growth arrest. 1215 14