Kyo S, Kanaya T, Ishikawa H, Ueno H, Inoue M
Department of Obstetrics and Gynecology, School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa 920, Japan.
Clin Cancer Res. 1996 Dec;2(12):2023-8.
Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends using an RNA component as a template. Extension of telomeric repeats by telomerase prevents telomere shortening with cell divisions and contributes to chromosomal stability, possibly leading to immortalization of the cells. In the present study, we determined the telomerase activity of gynecological tumors and cell lines using a newly developed non-radioisotope telomeric repeat amplification protocol. A total of 21 cell lines derived from cervical cancer, endometrial cancer, ovarian cancer, and choriocarcinoma was examined, and all lines were found to be positive for telomerase activity, although the activity varied among cell types. A total of 50 gynecological malignant tumors was also examined, and 10 of 12 (83%) cervical cancers, 12 of 13 (92%) endometrial cancers, 18 of 21 (86%) ovarian cancers, 2 of 2 tubal cancers, and 1 of 1 vulvar cancer were found to be positive for telomerase activity. A total of 88% of gynecological tumors tested was thus found to be telomerase positive. However, no significant correlation was observed between telomerase activity and clinical features for any tumor type, although ovarian tumors expressing high telomerase activity tended to be more invasive. In contrast to that in malignant tumors, telomerase expression was weak and less common in premalignant lesions, with 5 of 7 cervical intraepithelial lesions and 4 of 6 borderline ovarian tumors exhibiting faint activity. Nine benign uterine lesions were also examined, and all were negative for telomerase activity except 1 uterine myoma, which had a weak signal. Three benign ovarian cysts examined had weak telomerase activity. These findings suggest that telomerase activation is common in gynecological malignant tumors and may be a critical step in their pathogenesis. However, premalignant lesions and some types of benign tumors also express weak telomerase activity.
端粒酶是一种核糖核蛋白，它以RNA组分为模板，在染色体末端合成端粒DNA。端粒酶对端粒重复序列的延长可防止端粒随细胞分裂而缩短，并有助于染色体的稳定性，这可能导致细胞永生化。在本研究中，我们使用新开发的非放射性端粒重复序列扩增法，测定了妇科肿瘤及细胞系的端粒酶活性。共检测了21种源自宫颈癌、子宫内膜癌、卵巢癌和绒毛膜癌的细胞系，尽管活性在不同细胞类型中有所差异，但所有细胞系的端粒酶活性均为阳性。我们还检测了50例妇科恶性肿瘤，其中12例宫颈癌中有10例（83%）、13例子宫内膜癌中有12例（92%）、21例卵巢癌中有18例（86%）、2例输卵管癌中的2例以及1例外阴癌中的1例端粒酶活性呈阳性。因此，共88%的检测妇科肿瘤端粒酶呈阳性。然而，尽管表达高端粒酶活性的卵巢肿瘤往往更具侵袭性，但未观察到端粒酶活性与任何肿瘤类型的临床特征之间存在显著相关性。与恶性肿瘤相反，端粒酶表达在癌前病变中较弱且较少见，7例宫颈上皮内病变中有5例、6例卵巢交界性肿瘤中有4例呈现微弱活性。我们还检测了9例子宫良性病变，除1例信号较弱的子宫肌瘤外，其余均端粒酶活性阴性。检测的3例卵巢良性囊肿端粒酶活性较弱。这些发现表明，端粒酶激活在妇科恶性肿瘤中很常见，可能是其发病机制中的关键步骤。然而，癌前病变和某些类型的良性肿瘤也表达微弱的端粒酶活性。
