Cellular distribution of telomerase reverse transcriptase in human hepatocellular carcinoma.
OBJECTIVE
Telomerase is the enzyme that synthesizes telomeric DNA, and the activation of telomerase is closely related to cellular immortality. Telomerase activity has been reported in many human cancer tissues and is regulated by the expression of human telomerase reverse transcriptase (hTERT). The aim of the present study was to identify hTERT-expressing cells in human liver tissues and evaluate the feasibility of the hTERT promoter for gene therapy of hepatocellular carcinoma (HCC).


METHODS
The authors examined the cellular distribution of hTERT transcripts in surgically resected HCC by in situ hybridization.


RESULTS
Among 20 samples, hTERT expression was observed in 15 HCC. Transcripts of hTERT were homogenously distributed in the cytoplasm of HCC cells in nine of 15 cases; six of 15 cases displayed a heterogeneous staining pattern. All poorly differentiated HCC that expressed hTERT showed a homogenous pattern of staining. None of the non-cancerous hepatocytes were positive for the transcripts, but infiltrating lymphocytes were faintly stained. The homogenous expression of hTERT was also observed in the vascular invasion of HCC.


CONCLUSIONS
The results indicate that most HCC cells express hTERT RNA and that the promoter is a good candidate as a target for gene therapy. However, careful consideration must be taken concerning the potential effects on lymphocytes.
Onishi
Toru
T
Department of Medicine and Medical Science, Isotope center, Okayama University Graduate School of Medicine and Dentistry, Okayama Citizen's Hospital, Okayama, Japan.
Nouso
Kazuhiro
K
Higashi
Toshihiro
T
Toshikuni
Nobuyuki
N
Nakatsukasa
Harushige
H
Kobayashi
Yoshiyuki
Y
Uemura
Masayuki
M
Yumoto
Eiichiro
E
Fujiwara
Keishi
K
Sato
Shuichiro
S
Nakamura
Shinichiro
S
Yokoyama
Junko
J
Hanafusa
Tadashi
T
Shiratori
Yasushi
Y
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000628:therapy; D020134:Catalytic Domain; D003593:Cytoplasm / Q000201:enzymology; D004268:DNA-Binding Proteins; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D017403:In Situ Hybridization; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase