Telomerase activity and expression of telomerase genes in squamous dysplasia and squamous cell carcinoma of the esophagus.
BACKGROUND
Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Activation of telomerase plays a key role in the malignant transformation process. The aim of this study was to study the regulation of telomerase, and to explore the possibility of telomerase as a biomarker in squamous carcinogenesis of the esophagus.


METHODS
Twenty-nine esophageal squamous cell carcinomas (ESCC) and its corresponding adjacent normal tissues, and 47 epithelial squamous dysplasia tissues were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique for the mRNA expression of three major telomerase subunits: human telomerase RNA (hTR), telomerase protein component 1 (TP1), and human telomerase reverse transcriptase (hTERT) and by telomeric repeat amplification protocol assay (TRAP) for telomerase activity.


RESULTS
For the expression of hTR and TP1 mRNA, there were no significant differences among ESCC, dysplasia and normal tissues (P > 0.05). In contrast, hTERT mRNA expression was detected in 28 of 29 ESCC (96.6%), in 23 of 47 dysplasia (48.9%), and only in two of 29 normal tissues (7.5%). Telomerase activity was positive in 25 of 29 ESCC (86.2%), in 21 of 47 (44.7%) epithelial dysplasia tissues, and in none of normal tissue. All together, 95 of 105 cases (90.48%) were concordant for both results, i.e., telomerase activity positive and hTERT positive or telomerase activity negative and hTERT negative tissues, and telomerase activity correlated with hTERT mRNA expression (P < 0.001).


CONCLUSIONS
Higher telomerase activity and hTERT mRNA expression were shown during an early stage in the esophageal carcinogenesis. Activation of telomerase activity was strongly correlated with hTERT mRNA expression, suggesting hTERT is a major regulator of telomerase activity, and telomerase activation may play a critical role in esophageal carcinogenesis. Therefore, telomerase, especially hTERT can be used as a potential molecular biomarker of ESCC.
Yu
Hong-Ping
HP
Institute of Environmental Medicine, Tongji Medical College, Wuhan, Hubei Province, China.
Xu
Shun-Qing
SQ
Lu
Wen-Hong
WH
Li
Yuan-Yuan
YY
Li
Fang
F
Wang
Xiao-Li
XL
Su
Yan-Hua
YH
D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D004268:DNA-Binding Proteins; D004935:Esophageal Diseases / Q000201:enzymology* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase