Amioka Toru, Kitadai Yasuhiko, Hiyama Toru, Tanaka Shinji, Yoshihara Masaharu, Haruma Ken, Chayama Kazuaki
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biochemical Sciences, Hiroshima, Japan.
Oncol Rep. 2004 Jan;11(1):51-5.
Telomerase activity confers immortality to cells through stabilization of chromosomes and contributes to the development of most human cancers. Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of telomerase. Expression of hTERT mRNA has been reported to be correlated with telomerase activity. The purpose of this study was to investigate localization of hTERT mRNA in human esophageal precancerous and cancerous lesions by in situ mRNA hybridization with avidin-biotin staining. Ki-67 immunoreactivity was also examined. We analyzed 51 squamous cell carcinomas, 9 dysplasias and 60 normal mucosae. The integrity of mRNA in each sample was verified with a poly-d(T)20 probe. Seventy-eight samples (65%), including 35 carcinomas, 4 dysplasias and 39 normal mucosae, contained intact mRNA. At the single-cell level, hTERT was expressed at high levels in both the cytoplasm and nucleus. In all cases, the majority of cancer and dysplastic cells showed high levels of hTERT expression. In all 39 normal mucosae, basal cells expressed hTERT mRNA, and this was also observed in infiltrating lymphocytes. The distribution of cells expressing hTERT was similar to that of Ki-67-positive cells. These results suggest that overexpression of hTERT mRNA may be correlated with proliferative activity reflected by Ki-67 immunoreactivity and is an early event in carcinogenesis of the esophagus.
端粒酶活性通过稳定染色体赋予细胞永生性,并在大多数人类癌症的发生发展中起作用。人端粒酶逆转录酶(hTERT)是端粒酶的催化亚基。据报道,hTERT mRNA的表达与端粒酶活性相关。本研究的目的是通过抗生物素蛋白-生物素染色的原位mRNA杂交法,研究hTERT mRNA在人食管癌前病变和癌性病变中的定位。同时也检测了Ki-67免疫反应性。我们分析了51例鳞状细胞癌、9例发育异常和60例正常黏膜。用聚d(T)20探针验证每个样本中mRNA的完整性。78个样本(65%),包括35例癌、4例发育异常和39例正常黏膜,含有完整的mRNA。在单细胞水平上,hTERT在细胞质和细胞核中均高表达。在所有病例中,大多数癌细胞和发育异常细胞均显示hTERT高表达。在所有39例正常黏膜中,基底细胞表达hTERT mRNA,浸润淋巴细胞中也观察到这种情况。表达hTERT的细胞分布与Ki-67阳性细胞相似。这些结果表明,hTERT mRNA的过表达可能与Ki-67免疫反应性所反映的增殖活性相关,并且是食管癌发生的早期事件。