Elevated expression of hTERT is associated with dysplastic cell transformation during human oral carcinogenesis in situ.
OBJECTIVE
Telomerase is a ribonucleoprotein complex composed of the catalytic protein subunit (human telomerase reverse transcriptase or hTERT) and the RNA template. This enzyme activity is a necessary and rate-limiting step of cellular immortalization and could provide a unique marker of aberrant cells, which may selectively be targeted. The current study was undertaken to quantitatively determine the degree of telomerase activation during multistage oral carcinogenesis using paraffin-embedded tissue samples.


METHODS
hTERT expression level was quantitatively compared between normal and cancerous oral tissues by real-time reverse-transcription-PCR (RT-PCR). Also, the presence of hTERT transcript in individual cells was surveyed in the biopsy specimens with varying degrees of histopathology by in situ RT-PCR.


RESULTS
Low level of hTERT amplification was detected by real-time RT-PCR in most (11/13) normal human oral mucosa. hTERT expression was also detected in the majority (11/12) of squamous cell carcinoma tissues, and the level was significantly (P < 0.05) elevated, on the average, by a factor >6.9. By in situ RT-PCR, hTERT expression was not noted in normal epithelium (0/10) nor in mild dysplasia (0/7) but was detected in moderate dysplasia (4/5) and in those tissues with a higher grade of histopathology: severe dysplasia (3/3) and invasive carcinoma (4/4).


CONCLUSIONS
These results indicate that enhanced expression of telomerase activity occurs early during human oral carcinogenesis and support the critical role of telomerase in the development of human oral cancer.
Kim
H R
HR
Dental Research Institute, University of California, Los Angeles, 90095, USA.
Christensen
R
R
Park
N H
NH
Sapp
P
P
Kang
M K
MK
Park
N H
NH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase