Elevated activity of cyclin-dependent kinase 6 in human squamous cell carcinoma lines.
We have investigated the functional integrity of the retinoblastoma tumor suppressor pathway in five human squamous cell carcinoma lines. Elevated activity of cyclin-dependent kinase 6 (cdk6), a pRB kinase, was detected in all five squamous cell carcinoma lines. Overexpression of the cdk6 protein was detected in one of the five cell lines. The cdk6-specific inhibitor p18ink4C is expressed and associated with cdk6 in all five squamous cell carcinoma lines. In contrast, only very low levels of p16ink4A were detected in these cell lines. This may contribute to the elevated activity of cdk6 in these lines. Elevated activity of cdk6 may result in hyperphosphorylation of the retinoblastoma protein and, therefore, compromise its negative growth-regulatory activity.
Timmermann
S
S
Pathology Department, Harvard Medical School, Boston, Massachusetts 02115-5701, USA.
Hinds
P W
PW
Münger
K
K
D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005091:Exons; D016193:G1 Phase; D016147:Genes, Tumor Suppressor; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics; D015513:Oncogene Proteins / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; C493971:CDKN2C protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases