Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis.
OBJECTIVE
We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis.


METHODS
Three alternative splicing sites (alpha, beta, gamma) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in normal gastric mucosa, precancerous lesions and gastric cancer were detected by seminested RT-PCR. The expression of beta-site remaining ASV (beta(+) ASV) in specimens of precancerous lesions and specimens of gastric cancer was detected by SYBER Green real-time PCR.


RESULTS
The positive rate of alpha(+)beta(+)gamma(+) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7 vs. 40.0% and 0%, p < 0.05). The positive rates of other ASVs were not different among the 3 groups (p > 0.05). The positive rates of beta(+) ASVs (including alpha(+)beta(+)gamma(+) ASV, alpha-deletion ASV, gamma-deletion ASV, alphagamma-deletion ASV) were 11.1% in normal mucosa, 40.0% in precancerous lesions and 94.7% in gastric cancer (p < 0.05). SYBR Green real-time RT-PCR showed that the expression level of beta(+) ASV was 6.99 times higher in gastric cancer than in precancerous lesions.


CONCLUSIONS
hTERT alternative splicing pattern is different during gastric carcinogenesis. beta(+) ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions.
Xu
Jin-Heng
JH
Department of Biochemistry and Molecular Biology, Tianjin Medical University, Heping District, Tianjin, China.
Wang
Yu-Chuan
YC
Geng
Xin
X
Li
Yan-Yun
YY
Zhang
Wei-Ming
WM
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology; D005757:Gastritis, Atrophic / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000235:genetics*; D055815:Young Adult
D020033:Protein Isoforms; D012333:RNA, Messenger; D019098:Telomerase