Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of phorbol ester tumor promoters and related compounds on superoxide dismutase (SOD) and catalase were examined. The treatment of adult mouse skin with 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a sustained decrease in the basal levels of both SOD and catalase activities in the epidermis. A decline in SOD activity occurred within 3 h after application and the maximum effect was seen at 16--17 h. The decrease in SOD activity was always accompanied by a similar decline in the epidermal catalase activity. The alterations in both enzymes occurred against a high background of enhanced protein synthesis which indicates that the effect of TPA is selective for SOD and catalase. Other tumor promoters such as phorbol 12,13-dibutyrate and the non-phorbol tumor promoter anthraline also lowered the activities of both the enzymes. Mezerein, a resiniferonol derivative with weak promoting activity but a potent stage-II promoter, appeared to be more potent than TPA in lowering the basal levels. These results indicate that damage which favors neoplastic progression could occur in TPA-treated mouse skin due to the accumulation of free radicals resulting from low levels of SOD and catalase activity. In addition, the TPA-caused decrease in the levels of SOD and catalase was not prevented by either retinoic acid, fluocinolone acetonide, tosyl amino-2-phenylethyl chloromethyl ketone, or butylated hydroxytoluene, suggesting that inhibition of tumor promotion by these agents is not mediated through alterations in the levels of enzymatic activities which decrease free radical concentrations.
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PMID:Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promoters. 731 51

Cancer cells are commonly less differentiated than their normal progenitors; a phenotype that correlates with loss of specialized functions and an increased capability to self-renew. Melanoma is an ideal model to analyze cancer progression and differentiation since a well-characterized process of step-wise tumor progression has been defined. Our lab previously described a combinatorial in vitro treatment protocol to induce terminal differentiation of human melanoma cells using a low dose of the PKC activator Mezerein (Mez) combined with interferon-beta (IFN-beta), which also activates IFN-stimulated gene expression in addition to the re-differentiation program. In principle, using an alternate way to induce terminal differentiation not including IFN-beta would be more compatible with gene expression profiling. A higher concentration of Mez alone induced terminal differentiation of HO-1 human melanoma cells as measured by morphological, growth and biochemical assays. Pre-treatment with the PKC inhibitor GF109203x blocked changes associated with differentiation and inhibited the ability of Mez to force irreversible/terminal differentiation. By combining this efficient method of inducing terminal differentiation with microarray analyses we now identify potential regulators of this process and demonstrate utility of this novel in vitro model in which to study the molecular determinants and mechanisms of human melanoma differentiation.
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PMID:Model cell culture system for defining the molecular and biochemical events mediating terminal differentiation of human melanoma cells. 1884 38