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2001 Abstract: 1770 Telomerase and Colorectal Tumor Aggressiveness

2001 Digestive Disease Week

# 1770 Telomerase and Colorectal Tumor Aggressiveness
Aqeel Ghori, Bernhard Usselamann, Jill Barclay, Allan Morris, Ian Fraser, Coventry, UK,Barnstaple,UK

INTRODUCTION: Improvement in the treatment of colorectal cancer is dependent on the accuracy of the diagnosis, type and extent of tumour. The information provided by histological technique is not always precise. Telomerase a ribonucleoprotein enzyme prevent cellular senescence and thus induces immortality. This enzyme is expressed in 90% of colorectal cancer and is therefore of much interest especially as a prognostic indicator for the aggressiveness of the cancer.

AIM: The aim of our study was to evaluate whether elevated levels of telomerase can confer a selective growth advantage to colorectal tumour.

METHOD: A number of clones were derived from human colorectal carcinoma cell line HT29 and telomerase activity of the clones was determined. Tumour dose (TD50) of the parent HT29 cell line was determined by subcutaneous injection of graded number of cells in nu/nu athymic mice. Mice were examined three times in a week by digital palpation; the time to detection and development of the tumour to 10mm size was recorded. Tumourogenicity assay of the high and low telomerase-expressing clones was perfomed by using twenty athymic mice. Tumours once developed to end point was dissected out asseptically, tumour cells were re-isolated and telomerase activity was measured.

RESULTS: Our results show wide variation in telomerase expression in different clones, some shows negligible telomerase activity while in others there was two to three folds increase as compared to the parent HT29 sample. High telomerase expressing clone invaribly resulted in the development of an early and rapid growimg tumour ( Kaplan-Meier survival analysis). Re-isolation of the cells from tumour and subsequent telomerase measurement further confirmed that high levels of telomerase have been selected in vivo.

CONCLUSION: High telomerase activity seems to give relative growth advantage in colorectal cancer, suggesting more aggressive tumour select cell clones rich in telomerase. Hence, measurement of telomerase activity can help in predicting the future behavior of colorectal tumour. This observation may have implication in the treatment and follow up of colorectal cancer patients.

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