Telomerase activity and expression of telomerase RNA component and catalytic subunits in precancerous and cancerous colorectal lesions.
To investigate the role of telomerase activity in colorectal adenoma-carcinomas, telomerase activity, human telomerase RNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were quantitatively analyzed in human cancerous and precancerous colorectal tissues. Sixty-six colorectal tumor specimens, including 10 invasive carcinomas, 6 mucosal carcinomas and 50 adenomas were evaluated. Ten specimens of normal tissue were also included in the study. Telomerase activity was assayed by semiquantitative fluorescence using the TRAP-eze(TM) telomerase detection kit. Analysis of the expression of each telomerase subunit gene was performed by real-time PCR amplification. There was a positive correlation between histological atypia and telomerase activity (rho = 0.700, p < 0.0001), hTERT mRNA expression (rho = 0.603, p < 0.0001), and hTERC expression (rho = 0.290, p < 0.05). There was also a positive correlation between the levels of hTERT mRNA and telomerase activity (r = 0.455, p < 0.01). Significant differences in the levels of hTERT mRNA were shown between normal tissues and the adenomas (p < 0.05) and between the mucosal carcinomas and invasive carcinomas (p < 0.05). The values of hTERC expression in neoplastic tissues were significantly higher than in the normal tissues; however, there were no significant differences between the adenomas and the carcinomas. In summary, although upregulation of hTERC expression is an early event in adenoma development, hTERT mRNA expression is gradually upregulated during the adenoma-carcinoma sequence and may be a rate-limiting determinant of telomerase activity.
Naito
Y
Y
First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. ynaito@koto.kpu-m.ac.jp
Takagi
T
T
Handa
O
O
Ishikawa
T
T
Matsumoto
N
N
Yoshida
N
N
Kato
H
H
Ando
T
T
Takemura
T
T
Itani
K
K
Hisatomi
H
H
Tsuchihashi
Y
Y
Yoshikawa
T
T
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology* / Q000473:pathology; D000236:Adenoma / Q000201:enzymology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D019098:Telomerase / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase