In vitro and molecular characterization of canine prostatic cells and evaluation of antitumor response against target drugs

Abstract

The canis lupus familiaris is the only species besides humans that develops spontaneously prostate cancer (PC) associated with age and androgenic hormones. Like in humans, canine PC was associated to pre-neoplastic lesions: prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy (PIA). The prostatic diseases were frequently observed in humans and shows similar molecular and pathological characteristics in both species. Due to the importance of the dog as a model to PC study, this research aims to establish three cell lines of canine prostate carcinomas and perform the analysis of global gene expression using microarray platforms and identify possible potential therapeutic targets. The study of global gene expression in canine prostatic tissue is unprecedented and aims to identify the main pathways involved in canine CP. Using bioinformatic tools we will identify differentially expressed genes and potential therapeutic targets for conducting in vitro tests with their inhibitory drugs. In this study, we aim to identify the effect of these drugs on tumor cells, and to elucidate pathways inhibited by the respective drugs. Therefore, the present study is divided into two steps consisting of: 1- establishment and characterization of three cultures of prostatic cells to assess the global gene expression (identifying differentially expressed genes) and identification of potential therapeutic targets. In this step we will perform an expression compared between primary tumor and the cultures in passage 1 (P1), passage 5 (P5), passage 10 (P10) and passing (P15). 2 - After identifying drug targets genes, we will carry out gene and protein expression of the respective genes and subsequently validating with in vitro tests. (AU)