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)

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.
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PMID:Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity. 758 1

Ornithine decarboxylase (ODC) plays a rate-limiting role in polyamine biosynthesis and is intimately associated with cell proliferation and function. Although elevated levels of ODC mRNA, protein, and enzyme activity are consistently detected in transformed cells and tumors, the question remains as to whether ODC gene overexpression has a causative role in tumorigenesis. We have stably transfected NIH/3T3 fibroblasts with an expression construct containing human ODC complementary DNA under transcriptional control of the human beta-actin promoter. Cells transfected with the beta-actin/ODC DNA construct, designated NODC cells, and control transfectants, termed NLK cells, were analyzed for ODC gene expression and cell growth characteristics. ODC activity and mRNA levels were elevated 3-6-fold in NODC cells relative to NLK cells. NODC cells, in contrast to NLK control cells, are not contact inhibited, exhibit anchorage-independent growth, cycle more rapidly, and induce tumors in nude mice more efficiently and rapidly. These results directly establish a causative role for the misregulation of ODC gene expression in the acquisition of a transformation phenotype and provide a model to examine the interaction of ODC and other gene products in neoplastic development.
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PMID:Transformation of NIH/3T3 cells by ornithine decarboxylase overexpression. 849 25