[Type I insulin-like growth factor receptor antisense strategies in experimental breast cancer].
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.
Salatino
Mariana
M
Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina.
Schillaci
Roxana
R
Proietti
Cecilia J
CJ
Carnevale
Romina
R
Charreau
Eduardo H
EH
Elizalde
Patricia V
PV
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000820:Animal Diseases; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D008525:Medroxyprogesterone; D051379:Mice; D008807:Mice, Inbred BALB C; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1; D008525:Medroxyprogesterone