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

Pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited biological response to phorbol 12-myristate 13-acetate. The three responses examined were hyperplasia, induction of ornithine decarboxylase, and edema; the characteristics of inhibition depended on the specific response. Hyperplasia is the best short-term correlate of tumor promotion. Two or more pretreatments with 2.56 mumol (1 mg) prostratin, administered at intervals of 1-4 days, almost completely blocked the hyperplasia induced by phorbol 12-myristate 13-acetate applied 15 min to 6 h after the last pretreatment. Inducibility of hyperplasia was partially restored at 2 days and recovered by 4 days. Prostratin was more potent for inhibition of ornithine decarboxylase induction (50% inhibitory dose = 25.6 nmol) than it was for hyperplasia: the inhibition was largely attained by the first application, and the recovery from inhibition was slower (8 days). Edema was partially inhibited by prostratin (dose giving 50% of maximal inhibition = 512 nmol). We have previously demonstrated that prostratin is a protein kinase C activator. Our present results show that prostratin is a functional antagonist for a class of protein kinase C mediated responses. The findings emphasize the diversity of biological outcome for protein kinase C activators, presumably driven by the extensive heterogeneity in the protein kinase C pathway.
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PMID:Prostratin, a nonpromoting phorbol ester, inhibits induction by phorbol 12-myristate 13-acetate of ornithine decarboxylase, edema, and hyperplasia in CD-1 mouse skin. 191 57

The expression of epidermal growth factor receptor and transglutaminase type I, polyamine (putrescine, spermidine, and spermine) levels, ornithine decarboxylase activity, and micronuclei occurrence were assessed in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch model to elucidate the role and timing of changes in different growth and differentiation markers during carcinogenesis. DMBA (0.5%) in heavy mineral oil was applied to the right buccal pouch 3 times per wk for up to 16 wk; controls received heavy mineral oil alone. Hamsters were killed after 0, 4, 8, and 16 wk. Frozen tissue was chemically analyzed for polyamine levels and ornithine decarboxylase activity and was also used for immunohistochemical analysis of transglutaminase I. Paraffin-embedded sections were used for epidermal growth factor receptor immunohistochemical determinations and for micronucleated cell assays. Hyperplasia was detected by histological analysis at 4 wk, dysplasia with or without papillomatous changes at 8 wk, and squamous cell carcinoma at 16 wk. Epidermal growth factor receptor was not expressed in the normal buccal epithelial layer, at a moderate level in both the superficial keratin and basal cell layers in hyperplastic epithelium, and at very high levels in both dysplasia and squamous cell carcinoma. Transglutaminase I was expressed at a limited level in normal buccal mucosa, was expressed at a low level in the basal layer of hyperplastic lesions, was somewhat elevated in dysplasia, and was markedly enhanced in squamous cell carcinoma. Putrescine and spermidine levels and ornithine decarboxylase activity increased dramatically after 8 and 16 wk of DMBA. Micronucleated cells increased after 4 wk of DMBA treatment, that high level sustained during all stages of carcinogenesis. We suggest that these biological markers could be excellent intermediate end points in assessing the effects of various chemopreventive agents to be tested in the hamster buccal pouch model and in human clinical trials.
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PMID:Expression of epidermal growth factor receptor, polyamine levels, ornithine decarboxylase activity, micronuclei, and transglutaminase I in a 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model. 196 30