title: Telomerase reverse transcriptase (TERT) expression and proliferation in canine brain tumours.
abstract: Telomerase is a ribonucleoprotein enzyme complex that synthesizes telomere DNA. It is detected in 85-90% of malignant tumours in humans, but not in most somatic cells. Because telomerase plays a critical role in cell immortality, it represents an important target for anticancer therapies. We have previously shown that the dog is a potentially useful model for evaluating telomerase-based therapeutics. In this present study we analysed 93 canine brain tumours for telomerase reverse transcriptase (TERT) expression by immunohistochemistry. TERT immunoreactivity was detected in 16 of 50 grade 1 (32%) and 29 of 43 grade 2 tumours (67.4%), demonstrating a statistically significant association with histological grade (P = 0.00012). A subset of 51 tumours was also assessed for MIB-1 expression. The MIB-1 labelling index (LI) was found to correlate significantly with tumour grade, with a mean MIB-1 LI of 1.5% for grade 1 tumours, as compared with a mean MIB-1 LI of 21.7% for grade 2 tumours (P << 0.001). The MIB-1 LI was also significantly associated with TERT expression in all brain tumours (P << 0.001). These data further support the dog as a model for the preclinical development of telomerase-based therapeutics in brain tumours.
authors.affiliation: Institute for Comparative Medicine, University of Glasgow Veterinary School, UK. longsn@vet.upenn.edu
authors.forename: S
authors.initials: S
authors.lastname: Long
authors.forename: D J
authors.initials: DJ
authors.lastname: Argyle
authors.forename: C
authors.initials: C
authors.lastname: Nixon
authors.forename: I
authors.initials: I
authors.lastname: Nicholson
authors.forename: C
authors.initials: C
authors.lastname: Botteron
authors.forename: N
authors.initials: N
authors.lastname: Olby
authors.forename: S
authors.initials: S
authors.lastname: Platt
authors.forename: K
authors.initials: K
authors.lastname: Smith
authors.forename: G R
authors.initials: GR
authors.lastname: Rutteman
authors.forename: G C M
authors.initials: GC
authors.lastname: Grinwis
authors.forename: L
authors.initials: L
authors.lastname: Nasir
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004285:Dogs; D007150:Immunohistochemistry; D019098:Telomerase / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C509186:TERT protein, human; D019098:Telomerase