Analysis of IGF1R gene silencing effects in human adrenocortical tumors lines.

• Grant number: 10/09503-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2011
• End date: September 30, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ana Claudia Latronico Xavier
• Grantee: Tamaya Castro Ribeiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The insulin-like growth factor (IGF) system plays an important role in tumorigenesis. IGF1R overexpression has been demonstrated in a variety of tumors, suggesting that its expression is a fundamental prerequisite for cellular transformation. Recently, we demonstrated IGF1R overexpression in 66.6% and 20% of pediatric and adult tumors, respectively. Silencing of IGF1R by RNA interference (RNAi) has been described in lung, colon and liver tumors. This mechanism was able to decrease the cell proliferation rates and induce apoptosis, in addition to make tumor cells more sensitive to chemotherapeutic agents. In the present work we will induce IGF1R gene silencing by RNAi in cell lines of human adrenocortical tumors. Two distinct cell lines (NCI H295 and T7) will be cultivated and subjected to treatment with specific IGF1R RNAi. IGF-1R gene and protein expression will be determined by the techniques of real-time PCR and Western blot. The effects of in vitro silencing will be evaluated by cell proliferation assays and analysis of activity of caspases. Additionally, we will evaluate the expression of microRNA 145 and microRNA 100 in 50 adrenocortical tumors diagnosed in adults and children by real-time PCR technique. Inhibition of IGF1R gene expression represents a potential target and has a great interest in obtaining new and effective therapeutic options for human adrenocortical tumors.

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RIBEIRO, TAMAYA CASTRO; JORGE, ALEXANDER AUGUSTO; ALMEIDA, MADSON Q.; DE PAULA MARIANI, BEATRIZ MARINHO; NISHI, MIRIAN YUMI; MENDONCA, BERENICE BILHARINHO; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; LATRONICO, ANA CLAUDIA. Amplification of the Insulin-Like Growth Factor 1 Receptor Gene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression. BIOMED RESEARCH INTERNATIONAL, 2014. (10/09503-7)

RIBEIRO, TAMAYA CASTRO; LATRONICO, ANA CLAUDIA. Insulin-like growth factor system on adrenocortical tumorigenesis. Molecular and Cellular Endocrinology, v. 351, n. 1, SI, p. 96-100, MAR 31 2012. (10/09503-7)

RIBEIRO, T. C.; JORGE, A. A.; MONTENEGRO, L. R.; ALMEIDA, M. Q.; FERRAZ-DE-SOUZA, B.; NISHI, M. Y.; MENDONCA, B. B.; LATRONICO, A. C.. Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line. Hormone and Metabolic Research, v. 48, n. 7, p. 484-488, JUL 2016. (10/09503-7)

RIBEIRO, TAMAYA CASTRO; JORGE, ALEXANDER AUGUSTO; ALMEIDA, MADSON Q.; DE PAULA MARIANI, BEATRIZ MARINHO; NISHI, MIRIAN YUMI; MENDONCA, BERENICE BILHARINHO; BARISSON VILLARES FRAGOSO, MARIA CANDIDA; LATRONICO, ANA CLAUDIA. Amplification of the Insulin-Like Growth Factor 1 Receptor Gene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression. BIOMED RESEARCH INTERNATIONAL, v. 2014, p. 7-pg., 2014-01-01. (10/09503-7)

RIBEIRO, TAMAYA CASTRO; LATRONICO, ANA CLAUDIA. Insulin-like growth factor system on adrenocortical tumorigenesis. Molecular and Cellular Endocrinology, v. 351, n. 1, p. 5-pg., 2012-03-31. (10/09503-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RIBEIRO, Tamaya Castro. Analysis of expression and silencing of insulin-like growth factor 1 receptor in human adrenocortical tumors. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.