Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, Murakami Y, Kodama T, Piatyszek M A, Shay J W, Matsuura Y
Department of General Medicine, Hiroshima University School of Medicine, Japan.
Cancer Res. 1995 Aug 1;55(15):3258-62.
Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.
尽管在胃癌中已报道了许多基因改变，但尚不清楚所有胃肿瘤是否都具有无限增殖潜能，例如永生性。端粒酶的表达和端粒的稳定与肿瘤细胞获得永生性相伴；因此，在临床获取的肿瘤样本中检测端粒酶活性可能会提供重要信息，既可用作诊断标志物以检测临床材料中的永生癌细胞，也可用作患者预后的指标。使用基于聚合酶链反应（PCR）的检测方法对66例原发性胃癌的端粒酶活性进行了分析。大多数肿瘤（85%）显示端粒酶活性，但在10例肿瘤（15%）中未检测到端粒酶，其中8例为早期肿瘤。大多数具有端粒酶活性的肿瘤体积较大且处于晚期，包括有转移的情况。端粒酶活性可检测的肿瘤患者的生存率显著低于端粒酶活性不可检测的患者。在66例（21%）胃癌中有14例检测到端粒长度改变（端粒末端限制片段缩短/延长），且这14例均具有端粒酶活性。细胞DNA含量显示，所有22例非整倍体肿瘤均具有可检测的端粒酶活性。目前的结果表明，端粒酶激活可能是肿瘤发生多基因过程中的关键步骤，并且端粒酶在胃癌进展中常作为晚期事件被激活，但并非总是如此。
