Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis

A, Ly; François, Jean‐Christophe; Upegui-Gonzalez, Lia C.; B.Swiercz,; Bedel, Christophe; Duc, Huynh Thien; Bout, Daniel; Trojan, Jerzy

doi:10.1016/s0024-3205(00)00936-x

Cited by 13 publications

(8 citation statements)

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“…72 Additional efforts are being made to specifically inhibit the IGF-1R through adenoviral dominant negative IGF-1R, 73 IGF-1R antibodies, 74 IGF-1R antisense, 75 IGF-1R siRNAs 76 or IGF-I antisense. 77 The efficacy of IGF-1R inhibition in the clinical setting is yet unknown, and important questions remain about the potential toxicities from inhibiting normal IGF-1R or cross-reactivity with IR.…”

Section: Implications For Cancer Treatment and Preventionmentioning

confidence: 99%

Mechanisms by which IGF-I May Promote Cancer

Grimberg¹

2003

cbt

179

145

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Section: Implications For Cancer Treatment and Preventionmentioning

confidence: 99%

Mechanisms by which IGF-I May Promote Cancer

Grimberg¹

2003

cbt

179

145

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“…A significant body of evidence indicates that the IGF-I/IGF-IR axis interferes with immune recognition of tumor cells [13], [17], [23]. Indeed, triple helix-forming or antisense expression vectors targeting IGF-I induced a host immune response with up-regulation of immunogenic molecules and increased production of apoptotic cells [23], [24], [25] …”

Section: Introductionmentioning

confidence: 99%

Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model

et al. 2012

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Insulin-like growth factor I (IGF-I) and its type I receptor (IGF-IR) play significant roles in tumorigenesis and in immune response. Here, we wanted to know whether an RNA interference approach targeted to IGF-IR could be used for specific antitumor immunostimulation in a breast cancer model. For that, we evaluated short interfering RNA (siRNAs) for inhibition of in vivo tumor growth and immunological stimulation in immunocompetent mice. We designed 2′-O-methyl-modified siRNAs to inhibit expression of IGF-IR in two murine breast cancer cell lines (EMT6, C4HD). Cell transfection of IGF-IR siRNAs decreased proliferation, diminished phosphorylation of downstream signaling pathway proteins, AKT and ERK, and caused a G0/G1 cell cycle block. The IGF-IR silencing also induced secretion of two proinflammatory cytokines, TNF- α and IFN-γ. When we transfected C4HD cells with siRNAs targeting IGF-IR, mammary tumor growth was strongly delayed in syngenic mice. Histology of developing tumors in mice grafted with IGF-IR siRNA treated C4HD cells revealed a low mitotic index, and infiltration of lymphocytes and polymorphonuclear neutrophils, suggesting activation of an antitumor immune response. When we used C4HD cells treated with siRNA as an immunogen, we observed an increase in delayed-type hypersensitivity and the presence of cytotoxic splenocytes against wild-type C4HD cells, indicative of evolving immune response. Our findings show that silencing IGF-IR using synthetic siRNA bearing 2′-O-methyl nucleotides may offer a new clinical approach for treatment of mammary tumors expressing IGF-IR. Interestingly, our work also suggests that crosstalk between IGF-I axis and antitumor immune response can mobilize proinflammatory cytokines.

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“…9,2003 composed of multiple cytosine-adenine dinucleotides (CA repeats) 4,35 which may affect transcription activity; the length of the repeats is inversely correlated with transactivation. Besides CA repeats, the IGF-I PI also contains homopurine AG repeats 40 that play an important role in transcription 41 .…”

Section: Discussionmentioning

confidence: 99%

Analysis of Coding and Promoter Sequences of the IGF-I Gene in Children with Growth Disorders Presenting with Normal Level of Growth Hormone

Obrępalska‐Stęplowska¹,

Kędzia²,

Trojan³

et al. 2003

Journal of Pediatric Endocrinology and Metabolism

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The insulin-like growth factor-I (IGF-I) gene was analyzed in a population of children with growth disorders presenting normal GH and low IGF-I. We thus tried to detect any mutation in the IGF-I gene that could be responsible for short stature in children, using PCR, single-strand conformation polymorphism (SSCP) analysis, followed by DNA cloning and sequencing. We demonstrated in all examined children significant changes in the promoter region of the IGF-I gene (P1 IGF-I). Nucleotide sequence changes, such as CC-->GT and A-->G, and their localization are described. The results obtained excluded mutations in the coding sequence of the IGF-I gene. We conclude that testing the IGF-I P1 region, using PCR/SSCP analysis, could be useful in the diagnosis of growth disorders.

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Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis

Cited by 13 publications

References 0 publications

Mechanisms by which IGF-I May Promote Cancer

Mechanisms by which IGF-I May Promote Cancer

Small Interfering RNA Targeted to IGF-IR Delays Tumor Growth and Induces Proinflammatory Cytokines in a Mouse Breast Cancer Model

Analysis of Coding and Promoter Sequences of the IGF-I Gene in Children with Growth Disorders Presenting with Normal Level of Growth Hormone

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