Cell cycle proteins regulate the transitions from G1 to S and G2 to M phases. In higher eukaryotes, their function is controlled by intracellular cascades regulated by extracellular growth factors. We have studied in previously described transgenic mouse models for thyroid proliferative diseases the expression of the key proteins regulating the cell cycle by Western blotting and immunohistochemistry, and have correlated the observations with the known actions of the transgenes on the signal transduction cascades. In the adenosine A2a receptor model, the cyclic AMP pathway, upstream of the Rb family cell division block, is constitutively activated. In the model expressing HPV 16 E7 protein, the Rb-like proteins are inhibited. Cyclin-dependent kinases cdk4, cdk2 and cdc2, and the associated cyclins D, E and A have been studied. Cyclin D3 appears as the major cyclin D subtype expressed in mouse thyroid epithelial cells in normal and transgenic mice. In the adenosine A2aR model, all cell cycle proteins tested were accumulated. In the E7 model, all cell cycle proteins except for D-type cyclins and cdk4 were also accumulated. A similar pattern was observed in thyroids coexpressing both transgenes, suggesting a dominant effect of E7 over the consequences of the cAMP cascade activation. The cyclin-dependent kinase inhibitors p21cip1/waf1 and p27kip1 were not downregulated in these proliferating thyroids which suggest other roles than the inhibition of the cell cycle progression.
- MeSH
- buněčná diferenciace MeSH
- buněčný cyklus MeSH
- cyklin A metabolismus MeSH
- cyklin D MeSH
- cyklin E metabolismus MeSH
- cyklin-dependentní kinasa 2 MeSH
- cyklin-dependentní kinasa 4 MeSH
- cyklin-dependentní kinasy metabolismus MeSH
- cykliny metabolismus MeSH
- inhibitor p21 cyklin-dependentní kinasy MeSH
- inhibitor p27 cyklin-dependentní kinasy MeSH
- inhibitory enzymů metabolismus MeSH
- kinasy CDC2-CDC28 * MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- myši MeSH
- nádorové supresorové proteiny * MeSH
- nádory štítné žlázy metabolismus MeSH
- onkogenní proteiny virové genetika metabolismus MeSH
- Papillomavirus E7 - proteiny MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- proteinkinasa CDC2 metabolismus MeSH
- proteiny asociované s mikrotubuly metabolismus MeSH
- proteiny buněčného cyklu metabolismus MeSH
- proteiny metabolismus MeSH
- protoonkogenní proteiny * MeSH
- purinergní receptory P1 genetika metabolismus MeSH
- receptor adenosinový A2A MeSH
- štítná žláza metabolismus MeSH
- thyreoglobulin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
