1. [Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer].
- Author
-
Salatino M, Schillaci R, Proietti CJ, Carnevale R, Charreau EH, and Elizalde PV
- Subjects
- Adenocarcinoma drug therapy, Animal Diseases, Animals, Dose-Response Relationship, Drug, Female, Mammary Neoplasms, Experimental drug therapy, Medroxyprogesterone, Mice, Mice, Inbred BALB C, Oligodeoxyribonucleotides, Antisense metabolism, RNA, Messenger drug effects, Receptor, IGF Type 1 drug effects, Receptor, IGF Type 1 metabolism, Tumor Cells, Cultured, Adenocarcinoma metabolism, Mammary Neoplasms, Experimental metabolism, Oligodeoxyribonucleotides, Antisense therapeutic use, Receptor, IGF Type 1 antagonists & inhibitors, Receptors, Somatomedin metabolism
- Abstract
We addressed the effect of targeting type I insulin-like growth factor receptor (IGF-IR), with antisense strategies in 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.
- Published
- 2004