Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus.
BACKGROUND
Telomerase (reverse transcriptase) has been shown to play a role in the process of cellular immortalization.


METHODS
Telomerase activity was determined in 11 head and neck squamous cell carcinoma (SCCHN) cell lines. The effects of wild-type p16, p21, E2F-1, and p53 genes on telomerase activity were examined by introducing the wild-type genes into two SCCHN cell lines by means of a recombinant adenovirus.


RESULTS
We found elevated telomerase activity in 10 of the 11 SCCHN cell lines tested. When we infected Tu-138 and Tu-167 cell lines with wild-type p16, p21, E2F-1, and p53 genes, we found that p16 had little effect on telomerase activity. Both E2F-1 and p53 were known to induce apoptosis in SCCHN cell lines. Significantly reduced telomerase activity by p53 in both cell lines and E2F-1 in Tu-167 cells was in agreement with suppression of cell growth. Overexpression of p21 also exhibited reduction in telomerase activity.


CONCLUSIONS
We conclude from this study that overexpression of E2F-1 and p53 can reverse telomerase activity in SCCHN cell lines and that telomerase activity may be involved in cancer cell immortalization.
Henderson
Y C
YC
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Breau
R L
RL
Liu
T J
TJ
Clayman
G L
GL
D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000235:genetics*; D011995:Recombination, Genetic; D056465:Retinoblastoma-Binding Protein 1; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D019098:Telomerase; D015689:Oncogene Protein p21(ras)