Effect of elevated levels of ornithine decarboxylase on cell cycle progression in skin
| Autor: | S K, Gilmour, M, Birchler, M K, Smith, K, Rayca, J, Mostochuk |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Keratinocytes Apoptosis Cell Cycle Proteins Mice Transgenic Cyclin A Protein Serine-Threonine Kinases Ornithine Decarboxylase Gene Expression Regulation Enzymologic Mice Cyclins Proliferating Cell Nuclear Antigen Cyclin E CDC2-CDC28 Kinases In Situ Nick-End Labeling Animals Cells Cultured Skin Cell Nucleus Tumor Suppressor Proteins Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinases Enzyme Activation Genes ras Ki-67 Antigen Tumor Suppressor Protein p53 Microtubule-Associated Proteins Cell Division Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Cell growthdifferentiation : the molecular biology journal of the American Association for Cancer Research. 10(11) |
| ISSN: | 1044-9523 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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