Telomerase Activity with Concurrent Loss of Cell Cycle Regulation in Feline Post-traumatic Ocular Sarcomas

• Published in: Journal of comparative pathology 2005-11, Vol.133 (4), p.235-245
• Main Authors: Carter, R.T., Giudice, C., Dubielzig, R.R., Colitz, C.M.H.
• Format: Article
• Language: English
• Subjects: Animals; cat; Cat Diseases - enzymology; Cat Diseases - genetics; Cat Diseases - pathology; Cats; Cell Cycle - genetics; Cell Cycle - physiology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Eye - chemistry; Eye - enzymology; Eye - pathology; Eye Neoplasms - enzymology; Eye Neoplasms - pathology; Eye Neoplasms - veterinary; Female; Gene Expression Regulation, Neoplastic; Genes, p16; Genes, p53; Male; Mitosis; Neoplasms, Post-Traumatic - enzymology; Neoplasms, Post-Traumatic - pathology; Neoplasms, Post-Traumatic - veterinary; ocular sarcoma; Proliferating Cell Nuclear Antigen - genetics; Proliferating Cell Nuclear Antigen - metabolism; Sarcoma - enzymology; Sarcoma - pathology; Sarcoma - veterinary; telomerase; Telomerase - genetics; Telomerase - metabolism; Tumor Suppressor Protein p14ARF - genetics; Tumor Suppressor Protein p14ARF - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; tumour
• ISSN: 0021-9975; 1532-3129
• DOI: 10.1016/j.jcpa.2005.04.009

Paraffin wax-embedded ocular globes of cats with post-traumatic ocular sarcomas were examined for the presence of TERT, the active subunit of telomerase. The latter is a ribonucleoprotein complex essential for immortalization and expressed by most malignant tumours, germ line cells, lens epithelial cells, and some stem cells. Due to the frequent loss of cell cycle control with the increased expression of telomerase activity, post-traumatic ocular sarcomas were also examined for loss of p16 expression and alterations in p53, the findings being related to mitotic score, tumour grade, and proliferating cell nuclear antigen. These sarcomas expressed telomerase at a high frequency (62.5%); in addition, the majority showed alterations in cell cycle control, as evaluated by lack of p16 immunolabelling (66.7%). Alterations in p53 were the sole mechanism by which cell cycle control was dysregulated in only two tumours expressing TERT (13%). These findings suggest that p16, and not p53, represents the primary mechanism by which post-traumatic ocular sarcomas that express telomerase activity escape cell cycle control.