Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity
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 progest...
Guardado en:
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2004
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v23_n30_p5161_Salatino http://hdl.handle.net/20.500.12110/paper_09509232_v23_n30_p5161_Salatino |
| Aporte de: |
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paper:paper_09509232_v23_n30_p5161_Salatino |
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dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Antisense strategies Breast cancer IGF-IR antisense oligodeoxynucleotide epidermal growth factor receptor insulin receptor substrate 1 medroxyprogesterone acetate messenger RNA mitogen activated protein kinase oligodeoxynucleotide phosphorothioate phosphatidylinositol 3 kinase progesterone receptor protein p42 protein p44 somatomedin C receptor tyrosine antisense oligodeoxynucleotide messenger RNA mitogen activated protein kinase 1 phosphatidylinositol 3 kinase progesterone receptor somatomedin C receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast cancer cancer cell cancer growth cancer inhibition carcinogenesis cell proliferation control group controlled study dose response drug mechanism experimental model experimental mouse female in vivo study mouse nonhuman priority journal protein expression protein phosphorylation protein targeting signal transduction statistical significance animal Bagg albino mouse cancer transplantation cell culture cell division drug antagonism drug effect enzyme activation epithelium cell experimental neoplasm genetics metabolism pathology proto oncogene Animalia 1-Phosphatidylinositol 3-Kinase Animals Cell Division Dose-Response Relationship, Drug Enzyme Activation Epithelial Cells Female Genes, erbB-1 Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Neoplasm Transplantation Oligodeoxyribonucleotides, Antisense Receptor, IGF Type 1 Receptors, Progesterone RNA, Messenger Signal Transduction Tumor Cells, Cultured |
| spellingShingle |
Antisense strategies Breast cancer IGF-IR antisense oligodeoxynucleotide epidermal growth factor receptor insulin receptor substrate 1 medroxyprogesterone acetate messenger RNA mitogen activated protein kinase oligodeoxynucleotide phosphorothioate phosphatidylinositol 3 kinase progesterone receptor protein p42 protein p44 somatomedin C receptor tyrosine antisense oligodeoxynucleotide messenger RNA mitogen activated protein kinase 1 phosphatidylinositol 3 kinase progesterone receptor somatomedin C receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast cancer cancer cell cancer growth cancer inhibition carcinogenesis cell proliferation control group controlled study dose response drug mechanism experimental model experimental mouse female in vivo study mouse nonhuman priority journal protein expression protein phosphorylation protein targeting signal transduction statistical significance animal Bagg albino mouse cancer transplantation cell culture cell division drug antagonism drug effect enzyme activation epithelium cell experimental neoplasm genetics metabolism pathology proto oncogene Animalia 1-Phosphatidylinositol 3-Kinase Animals Cell Division Dose-Response Relationship, Drug Enzyme Activation Epithelial Cells Female Genes, erbB-1 Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Neoplasm Transplantation Oligodeoxyribonucleotides, Antisense Receptor, IGF Type 1 Receptors, Progesterone RNA, Messenger Signal Transduction Tumor Cells, Cultured Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| topic_facet |
Antisense strategies Breast cancer IGF-IR antisense oligodeoxynucleotide epidermal growth factor receptor insulin receptor substrate 1 medroxyprogesterone acetate messenger RNA mitogen activated protein kinase oligodeoxynucleotide phosphorothioate phosphatidylinositol 3 kinase progesterone receptor protein p42 protein p44 somatomedin C receptor tyrosine antisense oligodeoxynucleotide messenger RNA mitogen activated protein kinase 1 phosphatidylinositol 3 kinase progesterone receptor somatomedin C receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast cancer cancer cell cancer growth cancer inhibition carcinogenesis cell proliferation control group controlled study dose response drug mechanism experimental model experimental mouse female in vivo study mouse nonhuman priority journal protein expression protein phosphorylation protein targeting signal transduction statistical significance animal Bagg albino mouse cancer transplantation cell culture cell division drug antagonism drug effect enzyme activation epithelium cell experimental neoplasm genetics metabolism pathology proto oncogene Animalia 1-Phosphatidylinositol 3-Kinase Animals Cell Division Dose-Response Relationship, Drug Enzyme Activation Epithelial Cells Female Genes, erbB-1 Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Neoplasm Transplantation Oligodeoxyribonucleotides, Antisense Receptor, IGF Type 1 Receptors, Progesterone RNA, Messenger Signal Transduction Tumor Cells, Cultured |
| 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 phospliorothioate antisense oligodeoxynucleotides (AS[S]ODNs) to IGF-IR mRNA resulted in a significant inhibition of G4HD 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-Il 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 (IVIAPK) 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. |
| title |
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| title_short |
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| title_full |
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| title_fullStr |
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| title_full_unstemmed |
Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity |
| title_sort |
inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type i insulin-like growth factor receptor rnrna involves inactivation of erbbs, pi-3k/akt and p42/p44 mapk signaling pathways but not modulation of progesterone receptor activity |
| publishDate |
2004 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v23_n30_p5161_Salatino http://hdl.handle.net/20.500.12110/paper_09509232_v23_n30_p5161_Salatino |
| _version_ |
1768544373845262336 |
| spelling |
paper:paper_09509232_v23_n30_p5161_Salatino2023-06-08T15:54:49Z Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleptides to type I insulin-like growth factor receptor rnRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity Antisense strategies Breast cancer IGF-IR antisense oligodeoxynucleotide epidermal growth factor receptor insulin receptor substrate 1 medroxyprogesterone acetate messenger RNA mitogen activated protein kinase oligodeoxynucleotide phosphorothioate phosphatidylinositol 3 kinase progesterone receptor protein p42 protein p44 somatomedin C receptor tyrosine antisense oligodeoxynucleotide messenger RNA mitogen activated protein kinase 1 phosphatidylinositol 3 kinase progesterone receptor somatomedin C receptor animal cell animal experiment animal model animal tissue article breast adenocarcinoma breast cancer cancer cell cancer growth cancer inhibition carcinogenesis cell proliferation control group controlled study dose response drug mechanism experimental model experimental mouse female in vivo study mouse nonhuman priority journal protein expression protein phosphorylation protein targeting signal transduction statistical significance animal Bagg albino mouse cancer transplantation cell culture cell division drug antagonism drug effect enzyme activation epithelium cell experimental neoplasm genetics metabolism pathology proto oncogene Animalia 1-Phosphatidylinositol 3-Kinase Animals Cell Division Dose-Response Relationship, Drug Enzyme Activation Epithelial Cells Female Genes, erbB-1 Mammary Neoplasms, Experimental Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 Neoplasm Transplantation Oligodeoxyribonucleotides, Antisense Receptor, IGF Type 1 Receptors, Progesterone RNA, Messenger Signal Transduction Tumor Cells, Cultured 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 phospliorothioate antisense oligodeoxynucleotides (AS[S]ODNs) to IGF-IR mRNA resulted in a significant inhibition of G4HD 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-Il 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 (IVIAPK) 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. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09509232_v23_n30_p5161_Salatino http://hdl.handle.net/20.500.12110/paper_09509232_v23_n30_p5161_Salatino |