ABI3 and ABI3BP, characterization of in vitro interactions and investigation of the signaling pathway

• Grant number: 12/01346-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: June 01, 2012
• End date: February 29, 2016
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Janete Maria Cerutti
• Grantee: Lais Moraes de Godoy
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The analysis of SAGE libraries (Serial Analysis of Gene Expression) from Follicular Thyroid Adenoma (FTA), Follicular Thyroid Carcinoma (FTC) and normal tissue, identified more than 300 differentially expressed transcripts (P <0.001). Among these, the gene ABI3BP showed expression in libraries of normal tissue and FTA and no expression in CFT library. This gene was initially described by the double-hydride system for its possible interaction with ABI3 protein for the SH3 domain. Thus, we investigated the expression of ABI3 and ABI3BP in malignant and benign thyroid lesions and saw that its loss of expression is not restricted to the CFT, but also occur in other malignant lesions and that the expression levels of ABI3 and ABI3BP correlated positively in these lesions.In addition, we performed in vitro and in vivo studies that showed that the re-expression of these genes are involved in growth, cell viability and senescence processes. Finally, preliminary data evaluating the expression of ABI3 and ABI3BP in cell lines derived from thyroid follicular carcinoma (WRO and FTC 133) and metastasis to lymph nodes (FTC 236) or lung (FTC 238) suggest that ABI3 and ABI3BP may have a different role and modulate different signaling pathways in primary tumor and metastasis. So, the aims of this project are to investigate the interactions and cellular localization of ABI3 and ABI3BP, verify if post-translational modifications may interfere with the function of these proteins and to investigate signaling pathways potentially modulated by them in the primary tumor and metastasis. For this, ABI3 and ABI3BP are going to be cloned into expression vectors and transfect in the cell lines, WRO, FTC 133, FTC236 and FTC238. Clones permanent expressing recombinant proteins HA-ABI3 or ABI3BP-HIS are going be used in in vitro and in vivo assays. We believe that the data generated will clarify the roles of ABI3 and ABI3BP in the pathogenesis and progression of thyroid tumors. (AU)