Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line

T. C. Ribeiro; A. A. Jorge; L. R. Montenegro; M. Q. Almeida; B. Ferraz-de-Souza; M. Y. Nishi; B. B. Mendonca; A. C. Latronico

doi:10.1055/s-0042-108196

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2016; 48(07): 484-488
DOI: 10.1055/s-0042-108196

Endocrine Research

Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line

T. C. Ribeiro

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

A. A. Jorge

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

²Unidade de Endocrinologia Genética Laboratório de Endocrinologia Celular e Molecular, LIM/25, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

L. R. Montenegro

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

M. Q. Almeida

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

B. Ferraz-de-Souza

³Unidade de Doenças Osteometabólicas, Laboratório de Carboidratos e Radioimunoensaios LIM/18. Disciplina de Endocrinologia e Metabologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

M. Y. Nishi

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

B. B. Mendonca

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

,

A. C. Latronico

¹Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

› Author Affiliations

Abstract

Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling.

Key words

IGF system - IGF-1R - siRNA - adrenocortical tumors

Full Text

References

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