Timmermann S, Hinds P W, Münger K
Pathology Department, Harvard Medical School, Boston, Massachusetts 02115-5701, USA.
Cell Growth Differ. 1997 Apr;8(4):361-70.
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.
我们研究了五种人鳞状细胞癌系中视网膜母细胞瘤肿瘤抑制途径的功能完整性。在所有五种鳞状细胞癌系中均检测到细胞周期蛋白依赖性激酶6(cdk6,一种pRB激酶)的活性升高。在五个细胞系中的一个中检测到cdk6蛋白的过表达。cdk6特异性抑制剂p18ink4C在所有五个鳞状细胞癌系中均有表达并与cdk6相关。相比之下,在这些细胞系中仅检测到非常低水平的p16ink4A。这可能导致这些细胞系中cdk6活性升高。cdk6活性升高可能导致视网膜母细胞瘤蛋白的过度磷酸化,从而损害其负性生长调节活性。