Aida Junko, Izumiyama-Shimomura Naotaka, Nakamura Ken-Ichi, Ishii Akio, Ishikawa Naoshi, Honma Naoko, Kurabayashi Rie, Kammori Makoto, Poon Steven S S, Arai Tomio, Takubo Kaiyo
Research Team for Geriatric Diseases, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.
Hum Pathol. 2007 Aug;38(8):1192-200. doi: 10.1016/j.humpath.2006.11.023. Epub 2007 Jun 22.
We developed a novel method for evaluating telomere length in 6 cell types of noncancerous and cancerous mucosal tissues from 11 cases of gastric neoplasm using the quantitative fluorescence in situ hybridization method with telomere and centromere peptide nucleic acid probes. Our telomere length estimates were determined from the background-corrected telomere intensity divided by the background-corrected centromere intensity (telomere-to-centromere ratio). Our results indicated that telomere lengths in each of the cases studied were reduced in turn from fibroblasts to fundic gland cells, to glandular neck cells, and then to surface foveolar cells. However, the telomere lengths of intestinalized cells located among fundic glands were not always shorter than those of the other cell types, as reported previously by others. Helicobacter pylori infection was suggested to induce the telomere shortening seen in the fundic glands. Although the mean telomere lengths varied among the 8 gastric cancer cases, correlation of the telomere lengths with the Ki-67 labeling index was established after normalization with the fibroblast measurements. We conclude that our telomere-to-centromere ratio method can reliably estimate the telomere lengths of the 6 cell types in the gastric mucosa and clarifies the relationship between proliferative activity and the telomere length of cancer cells.
我们开发了一种新方法,使用端粒和着丝粒肽核酸探针的定量荧光原位杂交方法,对11例胃肿瘤的非癌性和癌性黏膜组织的6种细胞类型中的端粒长度进行评估。我们的端粒长度估计值是通过背景校正后的端粒强度除以背景校正后的着丝粒强度(端粒与着丝粒比率)来确定的。我们的结果表明,在所研究的每个病例中,端粒长度依次从成纤维细胞到胃底腺细胞、腺颈部细胞,再到表面小凹细胞逐渐缩短。然而,正如其他人之前所报道的,位于胃底腺之间的肠化生细胞的端粒长度并不总是比其他细胞类型的端粒长度短。幽门螺杆菌感染被认为会导致胃底腺中端粒缩短。虽然8例胃癌病例的平均端粒长度各不相同,但在用成纤维细胞测量值进行标准化后,端粒长度与Ki-67标记指数之间建立了相关性。我们得出结论,我们的端粒与着丝粒比率方法能够可靠地估计胃黏膜中6种细胞类型的端粒长度,并阐明增殖活性与癌细胞端粒长度之间的关系。