Demonstration of human telomerase RNA component (hTR) expression in normal, inflammatory and neoplastic colonic tissues by non-radioactive in situ hybridization

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Demonstration of human telomerase RNA component (hTR) expression in normal, inflammatory and neoplastic colonic tissues by non-radioactive in situ hybridization

 

Author: Lee, Wing-keung
Title: Demonstration of human telomerase RNA component (hTR) expression in normal, inflammatory and neoplastic colonic tissues by non-radioactive in situ hybridization
Degree: M.Sc.
Year: 2000
Subject: Telomerase
In situ hybridization
Hong Kong Polytechnic University -- Dissertations
Department: Multi-disciplinary Studies
Dept. of Nursing and Health Sciences
Pages: viii, 66 leaves : col. ill. ; 30 cm
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b1541794
URI: http://theses.lib.polyu.edu.hk/handle/200/4507
Abstract: Human telomeres, located at the chromosome ends, are essential for the chromosomal integrity and overall genomic stability. As cells divide, telomeres shorten continuously, leading to cell death. Telomerase is responsible for telomeres lengthening. Its activity is mainly found in proliferating cells such as germ cells and stem cells but not in most normal cells. In tumour cells, the telomerase activity is re-activated for telomere maintenance. The catalytic subunits of telomerase utilizes its intrinsic RNA component (hTR) as template to copy additional telomeric repeats at the ends of chromosomes. It is now becoming more widely accepted that re-activation of telomerase activity is a critical step for the continuing proliferation of cancer cells. Instead of detection of telomerase activity by standard telomeric repeat amplification protocol, this study aims to establish a non-radioactive, colorimetric in situ hybridization protocol to demonstrate the hTR expression in routine formalin-fixed, paraffin-embedded tissues. Having adopted this methodology, the expression of hTR in normal, inflammatory (ulcerative colitis and non-specific inflammation), and neoplastic (adenoma, adenocarcinoma and lymph node secondary to adenocarcinoma metatasis) colonic tissues was investigated. We found that hTR expression between normal and other conditions examined was significantly different (p<0.001). Therefore, demonstration of hTR can be used as a molecular biomarker for the differentiation between normal and pathological conditions, including inflammation and neoplasm. In addition, the hTR expression in the two pre-malignant conditions, adenoma and ulcerative colitis, was significantly different (p<0.05). In conclusion, overall findings showed that up-regulation of hTR expression was common in the pathological conditions studied. It is also suggested that hTR expression was up-regulated early in the hyper-proliferative stage during carcinogenesis.

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