Abstract:
We addressed the effect of targeting type I insulin-like growth factor receptor (IGF-IR), with antisense strategies in vivo growth of breast cancer cells. We used C4HD tumors from an experimental model of hormonal carcinogenesis in which medroxyprogesterone acetate induced mammary adenocarcinomas in Balb/c mice. Intratumor or systemic administration of phosphorothiolated antisense oligodeoxynucleotides (AS[S]ODN) to IGF-IR mRNA resulted in a significant inhibition of C4HD tumor growth. The antitumor effect was specific since inhibition of tumor growth was dose-dependent and no effect was observed in mice treated with sense S[S]ODN. Tumors from AS[S]ODN-treated mice showed a decrease in IGF-IR expression and in insulin receptor substrate-1 tyrosine phosphorylation. Activation of PI-3K/Akt, p42/p44 MAPK and ErbB-2 was abolished in tumors treated with AS[S]ODN. Progesterone receptor expression or activity remained invariable. This is the first demonstration that breast cancer growth can be inhibited by direct in vivo administration of IGF-IR AS[S]ODN.
Registro:
Documento: |
Artículo
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Título: | Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer |
Autor: | Salatino, M.; Schillaci, R.; Proietti, C.J.; Carnevale, R.; Charreau, E.H.; Elizalde, P.V. |
Filiación: | Inst. de Biologia y Medicina Exp., IBYME-CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
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Palabras clave: | Antisense strategies; Breast cancer; IGF-IR; antisense oligodeoxynucleotide; epidermal growth factor receptor 2; insulin receptor substrate 1; medroxyprogesterone acetate; messenger RNA; mitogen activated protein kinase; oligodeoxynucleotide phosphorothioate; progesterone receptor; protein kinase B; somatomedin C receptor; animal cell; animal experiment; animal model; article; breast adenocarcinoma; breast cancer; cancer cell; cancer growth; cancer inhibition; dose response; drug targeting; enzyme activation; hormonal carcinogenesis; in vivo culture; mouse; nonhuman; protein expression; protein phosphorylation; protein targeting; Adenocarcinoma; Animal Diseases; Animals; Dose-Response Relationship, Drug; Female; Mammary Neoplasms, Experimental; Medroxyprogesterone; Mice; Mice, Inbred BALB C; Oligodeoxyribonucleotides, Antisense; Receptor, IGF Type 1; Receptors, Somatomedin; RNA, Messenger; Tumor Cells, Cultured |
Año: | 2004
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Volumen: | 64
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Número: | 2
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Página de inicio: | 129
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Página de fin: | 134
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Título revista: | Medicina
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Título revista abreviado: | Medicina (Argentina)
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ISSN: | 00257680
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CODEN: | MEDCA
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CAS: | epidermal growth factor receptor 2, 137632-09-8; insulin receptor substrate 1, 175335-32-7; medroxyprogesterone acetate, 71-58-9; mitogen activated protein kinase, 142243-02-5; protein kinase B, 148640-14-6; Medroxyprogesterone, 520-85-4; Oligodeoxyribonucleotides, Antisense; Receptor, IGF Type 1, EC 2.7.1.112; Receptors, Somatomedin; RNA, Messenger
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v64_n2_p129_Salatino |
Referencias:
- Werner, H., Le Roith, D., New concepts in regulation and function of the insulin-like growth factors: Implications for understanding normal growth and neoplasia (2000) Cell Mol. Life Sci., 57, pp. 932-942
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- Balana, M.E., Labriola, L., Salatino, M., Activation of ErbB-2 via a hierarchical interaction between ErbB-2 and type I insulin-like growth factor receptor in mammary tumor cells (2001) Oncogene, 20, pp. 34-47
- Elizalde, P.V., Lanari, C., Molinolo, A.A., Involvement of insulin-like growth factors-I and -II and their receptors in medroxyprogesterone acetate-induced growth of mouse mammary adenocarcinomas (1998) J. Steroid Biochem. Mol. Biol., 67, pp. 305-317
- Lanari, C., Kordon, E., Molinolo, A., Pasqualini, C.D., Charreau, E.H., Mammary adenocarcinomas induced by medroxyprogesterone acetate: Hormone dependence and EGF receptors of BALB/c in vivo sublines (1989) Int. J. Cancer, 43, pp. 845-850
- Balana, M.E., Lupu, R., Labriola, L., Charreau, E.H., Elizalde, P.V., Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas (1999) Oncogene, 18, pp. 6370-6379
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Citas:
---------- APA ----------
Salatino, M., Schillaci, R., Proietti, C.J., Carnevale, R., Charreau, E.H. & Elizalde, P.V.
(2004)
. Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer . Medicina, 64(2), 129-134.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v64_n2_p129_Salatino [ ]
---------- CHICAGO ----------
Salatino, M., Schillaci, R., Proietti, C.J., Carnevale, R., Charreau, E.H., Elizalde, P.V.
"Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer "
. Medicina 64, no. 2
(2004) : 129-134.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v64_n2_p129_Salatino [ ]
---------- MLA ----------
Salatino, M., Schillaci, R., Proietti, C.J., Carnevale, R., Charreau, E.H., Elizalde, P.V.
"Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer "
. Medicina, vol. 64, no. 2, 2004, pp. 129-134.
Recuperado de https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v64_n2_p129_Salatino [ ]
---------- VANCOUVER ----------
Salatino, M., Schillaci, R., Proietti, C.J., Carnevale, R., Charreau, E.H., Elizalde, P.V. Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer . Medicina (Argentina). 2004;64(2):129-134.
Available from: https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257680_v64_n2_p129_Salatino [ ]