title: Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line.
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.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: T C
authors.initials: TC
authors.lastname: Ribeiro
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.|Unidade de Endocrinologia Genética Laboratório de Endocrinologia Celular e Molecular, LIM/25, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A A
authors.initials: AA
authors.lastname: Jorge
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: L R
authors.initials: LR
authors.lastname: Montenegro
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Almeida
authors.affiliation: Unidade 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.
authors.forename: B
authors.initials: B
authors.lastname: Ferraz-de-Souza
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M Y
authors.initials: MY
authors.lastname: Nishi
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: B B
authors.initials: BB
authors.lastname: Mendonca
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular, LIM/42, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology*; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1