Molecular prognostic markers in canine mast cell tumours

Abstract

Canine prostate carcinoma (PCa) is considered a good model for human PCa study and besides human dog is only specie that develops prostate cancer spontaneously. The study of spontaneous tumors in animal models has furthered our understanding of cancer pathogenesis,development, angiogenesis, and progression. The animal models of prostate cancer are critical for defining the molecular basis of the disease, elucidating the biology of tumor progression and the mechanisms of metastasis and developing effective treatment strategies. However, until recently, few animal models for the PCa existed, in part, because of the complexity of carcinogenesis and our relative inability to recapitulate these changes through genetic manipulation. The role of c-MYC oncogene and NKX3.1 and CDH1 tumor suppressor genes are well established in the carcinogenesis process of human prostate as well as the participation of the NKX3.1 and CDH1 hipermethylation, but in dogs there are few information about role of this genes in carcinogenic processo of prostate gland. In PhD scholarship project we evaluate proteic and genic expression of c-MYC, NKX3.1 and CDH1 and we found high expression of c-MYC and low expression of CDH1 and NKX3.1 in canine PCa. The last step of this research is evaluated methylation alterations in CDH1 and NKX3.1 and in last month we establish a primary cell culture of canine prostate cancer and this cells are frozen in liquid nitrogen. We will perform methylation analysis of CDH1 and NKX3.1 and if we find hypermethylation in promoter regions of these genes will be the first description of this alterations in the literature and we can show the similarity in human and canine prostate cancer. The experiments with cell culture was not propose in FAPESP scholarship but we belive that in vitro validation of methylation results incrised the impact of our research. The PhD student will perform an internship in Department of Biological Sciences at University of Guelph in partnership with the Institute for Comparative Cancer investigation (ICCI) and intends to hold the internship from May to August 2015 to learn epigenetic in vitro techniques and apply this technique in our cell culture and perform a functional assay. The idea of the functional assay is prove that methylation is a silencing mechanism in canine prostate cancer like in humans. (AU)