Toshikuni N, Nouso K, Higashi T, Nakatsukasa H, Onishi T, Kaneyoshi T, Kobayashi Y, Kariyama K, Yamamoto K, Tsuji T
First Department of Internal Medicine, Okayama University Medical School, Okayama-city, Japan.
Br J Cancer. 2000 Feb;82(4):833-7. doi: 10.1054/bjoc.1999.1008.
To know whether two protein components of human telomerase (human telomerase-associated protein 1 (hTEP1) and human telomerase reverse transcriptase (hTERT) are useful markers for telomerase activation in human liver diseases, we examined mRNA levels of these and telomerase activity in human liver samples. Twenty-three human hepatocellular carcinomas (HCCs) and corresponding adjacent livers were analysed for hTEP1 and hTERT expression by semiquantitative reverse transcription-polymerase chain reaction, and for telomerase activity by a telomeric repeat amplification protocol assay. Thirteen liver samples (ten HCCs and three dysplastic nodules) that were biopsied with 21-gauge needles were analysed for hTERT expression. hTEP1 was expressed in all samples examined. No correlation between hTEP1 expression and telomerase activity was observed. hTERT expression significantly correlated with telomerase activity (P< 0.001). The positivity of hTERT for HCC and corresponding non-cancerous liver was 100% and 30.4% respectively (P < 0.001). Seventy-four per cent (17/23) of HCCs showed strong hTERT expression, but none of the non-cancerous liver tissues did. hTERT expression of the 21-gauge needle biopsied specimens showed no significant difference from that of the surgical samples. The present study revealed that hTERT is strongly expressed in most HCCs, and that hTERT but not hTEP1 is a key component regulating telomerase activity in human liver.
为了确定人类端粒酶的两种蛋白质成分(人类端粒酶相关蛋白1(hTEP1)和人类端粒酶逆转录酶(hTERT))是否为人类肝脏疾病中端粒酶激活的有用标志物,我们检测了人类肝脏样本中这些成分的mRNA水平和端粒酶活性。通过半定量逆转录-聚合酶链反应分析了23例人类肝细胞癌(HCC)及其相应的癌旁肝脏组织中hTEP1和hTERT的表达,并通过端粒重复序列扩增协议分析检测了端粒酶活性。对13例用21号针活检的肝脏样本(10例HCC和3例发育异常结节)进行了hTERT表达分析。在所检测的所有样本中均检测到hTEP1的表达。未观察到hTEP1表达与端粒酶活性之间的相关性。hTERT表达与端粒酶活性显著相关(P<0.001)。HCC和相应非癌性肝脏组织中hTERT的阳性率分别为100%和30.4%(P<0.001)。74%(17/23)的HCC显示hTERT强表达,但非癌性肝组织均未显示。21号针活检标本的hTERT表达与手术样本的hTERT表达无显著差异。本研究表明,hTERT在大多数HCC中强烈表达,并且hTERT而非hTEP1是调节人类肝脏中端粒酶活性的关键成分。