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

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 adrenocorti...

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Published inHormone and metabolic research Vol. 48; no. 7; p. 484
Main Authors 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
Format Journal Article
LanguageEnglish
Published Germany 01.07.2016
Subjects
Adrenal Cortex - cytology
Apoptosis - genetics
Cell Line
Cell Proliferation
Down-Regulation - genetics
Gene Silencing
Humans
Receptor, IGF Type 1 - genetics
Receptor, IGF Type 1 - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Small Interfering - metabolism
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Summary: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.
ISSN:1439-4286
DOI:10.1055/s-0042-108196