Gene expression of telomerase related proteins in human normal oral and ectocervical epithelial cells.
We analyzed telomerase activities and gene expressions of telomerase components: hTERT, hTR, hTEP1, telomeric repeat binding factors: TRF1, TRF2, and c-myc, Max and Mad in human normal oral and ectocervical epithelial keratinocytes, comparing with those of squamous carcinoma cells and HPV16- or SV40-immortalized cells. Significant telomerase activity and hTERT expression were detected in primary keratinocytes. However, both were dramatically down-regulated during serial passages. The down-regulation of hTERT mRNA was associated with augmented expression of TRF1. Expression of c-myc was slightly decreased, whereas Mad was expressed in parallel with that of hTERT during passages. We also detected an alternate splicing of hTERT transcript in two of four cancer cells and normal aged epithelial cells. These results suggest that the senescence of normal oral and ectocervical keratinocytes is accompanied with up-regulation of TRF1 and down-regulation of telomerase activity due to transcriptional suppression of active form of hTERT in vitro.
Fujimoto
R
R
First Department of Oral and Maxillofacial Surgery, School of Dentistry, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima 770 8504, Japan.
Kamata
N
N
Taki
M
M
Yokoyama
K
K
Tomonari
M
M
Nagayama
M
M
Yasumoto
S
S
D017398:Alternative Splicing; D015139:Blotting, Southern / Q000379:methods; D002352:Carrier Proteins / Q000032:analysis*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology*; D009055:Mouth / Q000166:cytology*; D012313:RNA / Q000032:analysis*; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017421:Sequence Analysis / Q000379:methods; D019098:Telomerase / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000032:analysis*; D035321:Telomeric Repeat Binding Protein 1 / Q000032:analysis; D035341:Telomeric Repeat Binding Protein 2 / Q000032:analysis
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; D034501:Telomere-Binding Proteins; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase