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We are analyzing https://www.nature.com/articles/1207659.

Title:
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleotides to type I insulin-like growth factor receptor mRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity | Oncogene
Description:
The present study addresses the effect of targeting type I insulin-like growth factor receptor (IGF-IR) with antisense strategies in in vivo growth of breast cancer cells. Our research was carried out on C4HD tumors from an experimental model of hormonal carcinogenesis in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in Balb/c mice. We employed two different experimental strategies. With the first one we demonstrated that direct intratumor injection of phosphorothioate antisense oligodeoxynucleotides (AS[S]ODNs) to IGF-IR mRNA resulted in a significant inhibition of C4HD tumor growth. In the second experimental strategy, we assessed the effect of intravenous (i.v.) injection of AS [S]ODN on C4HD tumor growth. This systemic treatment also resulted in significant reduction in tumor growth. The antitumor effect of IGF-IR AS[S]ODNs in both experimental protocols was due to a specific antisense mechanism, since growth inhibition was dose-dependent and no abrogation of tumor proliferation was observed in mice treated with phosphorothioate sense ODNs (S[S]ODNs). In addition, IGF-IR expression was inhibited in tumors from mice receiving AS[S]ODNs, as compared to tumors from control groups. We then investigated signal transduction pathways modulated in vivo by AS[S]ODNs treatment. Tumors from AS[S]ODN-treated mice of both intratumoral and intravenous protocols showed a significant decrease in the degree of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation. Activation of two of the main IGF-IR signaling pathways, phosphatidylinositol 3-kinase (PI-3K)/Akt and p42/p44 mitogen-activated protein kinases (MAPK) was abolished in tumors growing in AS[S]ODN-treated animals. Moreover, ErbB-2 tyrosine phosphorylation was blocked by in vivo administration of AS[S]ODNs. On the other hand, we found no regulation of either progesterone receptor expression or activity by in vivo AS[S]ODNs administration. Our results for the first time demonstrated that breast cancer growth can be inhibited by direct in vivo administration of IGF-IR AS[S]ODNs.
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Keywords {🔍}

cancer, breast, res, nature, mol, growth, elizalde, access, baserga, article, biol, oncogene, receptor, cell, content, vivo, igfir, research, assodns, natl, sci, cookies, antisense, charreau, tumor, proc, acad, usa, endocrinology, privacy, progesterone, salatino, tumors, experimental, open, rubin, lee, lange, data, inhibition, signaling, pathways, proietti, mice, chem, ilan, endocrinol, coppola, sell, horwitz,

Topics {✒️}

nature portfolio permissions reprints privacy policy nature advertising scientific promotion social media author information authors research igf-1r antibody cixutumumab author correspondence igf-ir mrna resulted erbb-2-positive breast cancer insulin receptor substrate-1 growth factor receptor personal data springerlink instant access instituto de biología progesterone receptor expression progesterone receptor activity data protection permissions breast cancer growth cancer gene ther isabel frahm induced mammary adenocarcinomas breast cancer cells privacy igf-ir expression c4hd tumor growth tumor-suppressor mir-16 breast cancer res explore content subscription content kull jr fc specific antisense mechanism european economic area present study addresses institutional subscriptions read e3 ligase nedd4 sanatorio mater dei accepting optional cookies myers jr mg roberts jr ct journals search log phosphorothioate antisense oligodeoxynucleotides ignar-trowbridge dm overcomes trastuzumab resistance cordo russow béguelinp article salatino

Questions {❓}

  • Nuclear ErbB-2: a Novel Therapeutic Target in ErbB-2-Positive Breast Cancer?

Schema {🗺️}

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         Apoptosis
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         name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Mariana Salatino
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            name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490
            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Roxana Schillaci
      affiliation:
            name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490
            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Cecilia J Proietti
      affiliation:
            name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490
            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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            name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490
            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Isabel Frahm
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      name:Alfredo A Molinolo
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               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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               name:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI), Argentina
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            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Patricia V Elizalde
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            name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490
            address:
               name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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      name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
      name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
      name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
      name:Servicio de Patología, Sanatorio Mater Dei, Buenos Aires, Argentina
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      name:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI), Argentina
      name:Laboratory of Molecular Mechanisms of Carcinogenesis, Instituto de Biología y Medicina Experimental (IBYME), CONICET, Obligado 2490, Buenos Aires, Argentina
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