• MeSH
• adenosintrifosfatasy MeSH
• antigeny MeSH
• cytotoxické T-lymfocyty MeSH
• melanom imunologie   MeSH
• Publikační typ
• přehledy MeSH

The p16Ink4/CDKN2, D-type cyclins, their partners Cdk4/Cdk6, and pRb constitute a G1 regulatory pathway commonly targeted in tumorigenesis. Genetic, immunochemical, and functional cell cycle analyses showed abnormalities of this pathway in each of 22 human melanoma cell lines examined. Normal melanocytes and all melanoma lines expressed Cdk4, Cdk6, and cyclins D1 and D3. The tumor suppressors p16Ink4/CDKN2 and pRb were lost in 17 and 4 cases, respectively, due to various genetic mechanisms, including transcriptional block of p16 and nonsense mutations of RB1. Ectopic expression of p16 prevented S-phase entry of Rb+/p16- but not Rb-deficient melanoma lines. The SK29-MEL-1 cell line harboring an R24C mutation in Cdk4 expressed wild-type pRb and overabundant p16, the latter preventing endogenous Cdk6 but not Cdk4 from associating with cyclin D1. Microinjection of cyclin D1-neutralizing antibody arrested the SK29-MEL-1 cells in G1, whereas pl6 did not, indicating that the cyclin D1/Cdk4-R24C complex is required for G1 progression, and the resistance of the complex to p16 in vivo. These data strongly support the candidacy of Cdk4 as a novel proto-oncogene, provide further evidence for the p16-cyclin D/Cdk-pRb pathway as a functional unit, and suggest that deregulation of this checkpoint may represent a common step in the multistep progression of sporadic malignant melanomas.

• MeSH
• cyklin D MeSH
• cyklin-dependentní kinasa 4 MeSH
• cyklin-dependentní kinasy genetika   fyziologie   MeSH
• cykliny genetika   fyziologie   MeSH
• delece genu MeSH
• G1 fáze fyziologie   MeSH
• geny retinoblastomu MeSH
• inhibitor p16 cyklin-dependentní kinasy MeSH
• lidé MeSH
• melanom etiologie   genetika   patofyziologie   MeSH
• molekulární sekvence - údaje MeSH
• nádorová transformace buněk genetika   MeSH
• nádorové buňky kultivované MeSH
• polymerázová řetězová reakce MeSH
• progrese nemoci MeSH
• protoonkogenní proteiny * MeSH
• protoonkogeny MeSH
• retinoblastomový protein fyziologie   MeSH
• sekvence nukleotidů MeSH
• signální transdukce fyziologie   MeSH
• transportní proteiny genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH