Abstract:
:Cell lines developed from head and neck squamous cell carcinomas exhibit variable responses to the negative regulatory effects of transforming growth factor beta (TGF beta) on cell growth. To analyse the effects of TGF beta on regulators of cell cycle progression, we characterised cell lines derived from head and neck squamous cell carcinoma (HNSCC) for their biological sensitivities to TGF beta, growth inhibition, then examined the effects of TGF beta treatment on the expression and activity of cyclin dependent kinases (CDKs) and inhibitors of these kinases. Western blot analysis of cell lysates from untreated or TGF beta-treated cultures showed no alterations in expression of CDK2, CDK4, CDK6 or cyclin E in cell lines which were either sensitive (HaCaT, HN6) or refractory (HN12, HN30) to the growth-inhibitory effects of TGF beta. However, treatment of cells with TGF beta resulted in a several fold increase in cellular levels of p21 (WAF1/Cip1), irrespective of biological response. Immune complex in vitro kinase assays demonstrated that the activity of CDK2 was inhibited by exposure to ligand in each case, confirming that a TGF beta signalling pathway which regulates kinase activity was intact in these cell lines. The data suggest that cellular factors expressed in HN12 and HN30 enable these cells to override TGF beta-mediated inhibition of CDK2 activity and allow cell cycle progression. This may represent an important mechanism which allows cells to evade growth arrest during malignant progression.
journal_name
Oral Oncoljournal_title
Oral oncologyauthors
Lesaca EE,Ensley JF,Yeudall WAdoi
10.1016/s1368-8375(97)00023-7subject
Has Abstractpub_date
1998-01-01 00:00:00pages
52-7issue
1eissn
1368-8375issn
1879-0593pii
S1368-8375(97)00023-7journal_volume
34pub_type
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