Advanced search
Start date
Betweenand

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 Investigator: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.