The role of MYBL1 and MYBL2 on the androgen-independent prostate cancer cell behavior

• Grant number: 13/23123-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 20, 2014
• End date: September 19, 2014
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Rafaela da Rosa Ribeiro
• Supervisor: Gary H. Karpen
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Lawrence Berkeley National Laboratory, United States
• Associated to the scholarship: 12/07512-4 - Sequential gene expression in response to androgen deprivation: orchestrating secretion activity, proliferation and cell death in the rat ventral prostate, BP.DR

Abstract

Advanced stages of prostate cancer (PCa) involves growth in androgen-depleted environment, and the mechanisms underlying progression to androgen-independent prostate cancer following androgen deprivation or blockade therapies has attracted much attention. DNA microarray analysis conducted to determine comprehensive profiling of gene expression and extensive bioinformatics unveiled that Mybl1 and Mybl2, two members of Myb gene family, were up-regulated after castration. Myb plays important roles in mammary gland tumorigenesis, and has recently implicated in the pathogenesis and procession of prostate cancer and also it was suggested that it may activate signal transductions, increase cell proliferation, cell motility, and downregulation of onco-suppressor and apoptogenic genes and thereby keep the cancer cells alive. In this project we will investigate the underlying mechanisms of MYBL1 and MYBL2 on the androgen-independent prostate cancer progression by examining specific targets of gene regulation by MYB, using high resolution chromatin immunoprecipitation and third generation sequencing. We have investigated Myb expression and activation in three prostate cancer cell lines, and found LNCaP express Mybl2, which was found in its phosphorylated active form in the cell nucleus. The laboratory chosen for developing this research has a long tradition in such techniques and is locates in a comprehensive cancer research center. (AU)