Onishi Toru, Nouso Kazuhiro, Higashi Toshihiro, Toshikuni Nobuyuki, Nakatsukasa Harushige, Kobayashi Yoshiyuki, Uemura Masayuki, Yumoto Eiichiro, Fujiwara Keishi, Sato Shuichiro, Nakamura Shinichiro, Yokoyama Junko, Hanafusa Tadashi, Shiratori Yasushi
Department of Medicine and Medical Science, Isotope center, Okayama University Graduate School of Medicine and Dentistry, Okayama Citizen's Hospital, Okayama, Japan.
J Gastroenterol Hepatol. 2003 Oct;18(10):1168-74. doi: 10.1046/j.1440-1746.2003.03137.x.
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).
The authors examined the cellular distribution of hTERT transcripts in surgically resected HCC by in situ hybridization.
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.
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.
端粒酶是合成端粒DNA的酶，端粒酶的激活与细胞永生化密切相关。许多人类癌症组织中都报道了端粒酶活性，其受人类端粒酶逆转录酶（hTERT）表达的调控。本研究的目的是鉴定人类肝脏组织中表达hTERT的细胞，并评估hTERT启动子用于肝细胞癌（HCC）基因治疗的可行性。
作者通过原位杂交检测手术切除的肝癌组织中hTERT转录本的细胞分布。
在20个样本中，15个肝癌组织观察到hTERT表达。15例中有9例hTERT转录本均匀分布于肝癌细胞的细胞质中；15例中有6例呈现异质性染色模式。所有表达hTERT的低分化肝癌均显示均匀的染色模式。非癌性肝细胞的转录本均为阴性，但浸润淋巴细胞有微弱染色。在肝癌的血管侵犯中也观察到hTERT的均匀表达。
结果表明，大多数肝癌细胞表达hTERT RNA，该启动子是基因治疗靶点的良好候选者。然而，必须仔细考虑对淋巴细胞的潜在影响。
