Telomerase: A Potential Diagnostic and Therapeutic Tool in Canine Oncology

Abstract

Abstract. In recent years there has been considerable interest in telomerase as a target for therapeutic intervention in oncology. This largely stems from the vast number of studies that have demonstrated expression and activity of the enzyme telomerase in the majority of human cancer tissues with little or no activity detectable in normal somatic tissues. These studies have led to an interest in the role of telomerase in cancers associated with domesticated species, in particular tumors that affect dogs. This article reviews the biology of telomerase and the biological significance of telomerase activity in canine tumors and discusses the clinical implications of telomerase expression in canine cancers with regard to therapeutics and diagnostics.

Immunohistochemical expression of dogTERT in canine testicular tumours in relation to PCNA, ki67 and p53 expression.

“…Tissue distribution of telomerase activity in the dog is similar to the one in humans where it is largely confined to cancer cells or cells with high proliferative potential while it is absent from most normal somatic tissues (Argyle and Nasir 2003). Additionally the immunodetection of telomerase is now being recognised as a necessary approach to precisely elucidate its roles in senescence and tumorigenesis (Wu et al 2006).…”

“…Using the NCL-hTERT antibody, immunoreaction was detected in the majority of the tumours investigated. This is not surprising since nucleolin and telomerase are known to interact and share a similar pattern of expression (Argyle and Nasir 2003). Additionally, nucleolin's ability to bind to the human telomeric DNA sequence, TTAGGG, has also been reported (Ishikawa et al 1993;Pollice et al 2000).…”

“…In humans, telomerase activity is detected in germ lines and haematopoietic cells (Kim et al 1994), which constantly undergo cell division, but not in differentiated somatic cells. Recent studies support the notion that the dog is the most appropriate animal model to study human telomerase (Nasir et al 2001;Argyle and Nasir 2003). Canine TERT has been detected immunohistochemically in many canine tumour types using commercially available anti-hTERT antibodies (Renwick et al 2006;Long et al 2006;Panarese et al 2006;Colitz et al 2006;Mandrioli et al 2007;Zarfoss et al 2007;Zavlaris et al 2009) and the evaluation of its expression has now been recognized as an essential approach to the study of cell proliferation and tumorigenesis.…”

Keçilerin Enzootik Intranazal Tümörlerinde Telomeraz Enziminin Düzeyinin Belirlenmesi

“…This activity protects the integrity of chromosomes from digestion by exonucleases, fusion to the neighboring chromosomes and occurring the chromosomal defects [29,30] . Possible relation between carcinogenesis and telomere dysfunctions was reported [31,32] . Previous studies cataloging TERT expression and telomerase activity reported potent suppression in human somatic tissues, while robust expression and activity in germ cells and cancer cells.…”

“…Progressive telomere shortening from cell division provides a barrier for tumor progression. However, one of the hallmarks of advanced malignancies is continuous cell growth and this almost universally correlates with the reactivation of telomerase [32] . Many authors suggested that determination of telomerase activity may serve as a diagnostic and prognostic tool in oncology.…”