33 Malaysian J Pathol 2007; 29(1) : 33 – 35 Telomerase activation in neoplastic cell immortalization and tumour progression Lai Meng LOOI MD, FRCPath, Min-Hwei NG BSc, MSc and Phaik-Leng CHEAH MD, FRCPath Department of Pathology, Faculty of Medicine, University of Malaya, Malaysia Abstract The unique ability of tumour cells to proliferate indefinitely is crucial to neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subject to a “mitotic clock,” a phenomenon that has been linked to telomeric shortening after each round of cell replication, so that eventually the loss of genetic material reaches a critical stage and the cells undergo senescence and cell death. A study was conducted to investigate the role of telomerase, an RNA-containing enzyme that restores the telomere length, in the neoplastic cell immortalization and progression process. Fresh human tissue samples taken from excision specimens received by the Department of Pathology, University of Malaya Medical Centre, were investigated for telomerase activity using a commercial Telomerase PCR-ELISA kit (Boehringer Mannheim). Specimens comprised 33 breast lesions (10 infiltrating breast adenocarcinoma, 13 fibroadenoma and 10 non-neoplastic breast tissue), 27 colonic lesions (17 colonic adenocarcinoma and 10 non-neoplastic colonic mucosa) and 42 cervical lesions (20 cervical carcinoma and 22 non-neoplastic cervical tissues). Telomerase activity was found in 6 (60%) of 10 breast carcinomas, 6 (46%) of 13 fibroadenomas, none of the 10 non- neoplastic breast samples, 3 (17.6%) of 17 colon carcinomas and none of the 10 non-neoplastic colonic mucosal samples, 12 (60%) of 20 cervical carcinoma and 3 (13.6%) of 22 non-neoplastic cervical samples. 5/10 (50%) Stage I, 4/7 (57%) Stage II, 2/2 (100%) Stage III and 1/1 (100%) Stage IV cervical carcinomas showed telomerase activity. These findings support a contributory role for telomerase in tumourigenesis with activation occurring from neoplastic transformation and increasing with tumour progression. Key words: telomerase, TRAP-ELISA, breast cancer, colon cancer, cervical cancer, cell immortalization Address for correspondence and reprint requests: Professor L.M. Looi, Department of Pathology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia INTRODUCTION Tumour cells have the unique ability to proliferate indefinitely, hence achieving a state of immortality. This is crucial for neoplastic progression as it allows these cells to express the aggressive properties of cancer without the censure of physiological ageing. This is in contrast to normal somatic cells which are subjected to biological ageing and programmed cell death, often referred to as the “mitotic clock,” a phenomenon that has been linked to the repetitive loss of telomeric material with the mitotic cycle. In normal somatic cells, the telomeric tips of chromosomes shorten with every round of cell replication. 1 Eventually, the loss of genetic material reaches a critical level and cells enter a stage of senescence and eventual cell death. Telomerase is a ribonucleoprotein which is capable of synthesizing telomeric DNA onto chromosomal ends using a segment of its RNA component as a template. 2,3 First discovered in Tetrahymena and other eukaryotes in 1989, it has been convincingly demonstrated in humans in 1995. Recent studies indicate strong telomerase activity in germ cells (ovary and testis) and various tumours but weak or no activity in normal somatic tissues. 3,4 This has led to the notion that telomerase plays a key role in the neoplastic cell immortalization process by restoring telomere length. 5,6 This study was conducted to compare telomerase activity in benign and malignant human tumours and their non-neoplastic tissue counterparts, to gain an insight into the role of telomerase in the progression of human cancers.