STUDY OF HISTONE ACETYLATION STATUS IN GASTRIC CARCINOGENESIS

• Grant number: 09/08046-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2010
• Effective date (End): July 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Marilia de Arruda Cardoso Smith
• Grantee: Fernanda Wisnieski
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 09/07145-9 - Genetic and epigenetic aspects in gastric carcinogenesis, AP.TEM

Abstract

Gastric cancer is the fourth most prevalent and the second cause of cancer death worldwide. Nowadays, Brazil is in the fourth most prevalent rank in gastric cancer in Latin America. Epigenetic dysregulation is central to initiation and progression of some cancers. Chromatin remodeling, including histone acetylation, regulates gene expression without changing the sequence of DNA. To analyze whether histone acetylation is involved with carcinogenesis, two gastric cell lines will be treated with deacetylation agent and then, samples before and after treatment will be analyzed by microarray in the current study. After microarray screening, differentially expressed genes will be evaluated in 50 normal and in 50 tumoral gastric samples by qRT-PCR. Expression of genes involved in histone modifications machinery, HDAC1, HDAC2, HDAC3, PCAF and GCN5, will be also measured by qRT-PCR. Histone H3K9 acetylation status will be evaluated in differently expressed genes by ChIP. Variables associated to gene expression and modifications of histone acetylation status will be associated to sex, age, tumor location, H. pylori, tumor extension, limph node metastasis, distant metastasis and histopathologic type of gastric adenocarcinoma. The current study will originate new and better biological information to understand the etiology and physiopathology of gastric cancer with potential medical implication.