Treatment of human breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor inhibits cell growth, suppresses tumorigenesis, alters the metastatic potential, and prolongs survival in vivo

The type I insulin-like growth Factor receptor (IGF-IR) plays an important role in the growth and transformation of breast cancer cells. In this study , we investigated the effects of treatment with an antisense ICF-IR constru ct on cells from the highly metastatic estrogen receptor-negative human bre ast cancer cell line MDA-MB-435s. The cells carrying the antisense IGF-IR h ad a markedly reduced expression of ICF-IR, had a significant decrease in c ell proliferation, and lost the ability to form colonies in sort agar. Ther e was a delay in tumor formation and a dramatic reduction in tumor size whe n cells carrying the antisense ICF-IR were injected into either nude or sev ere combined immunodeficient (scid) beige mice. We have also provided data that show that the scid beige mouse is a more suitable model for studying m etastasis of the MDA-MB-435s cells. All of the scid beige mice injected wit h cells carrying the control construct had metastasis to the lungs, whereas lungs from the nude mice had no apparent metastatic sites after 11 weeks. When cells carrying antisense IGF-IR were injected subcutaneously in scid b eige mice, the animals had a significant increase in survival compared with mice injected with cells carrying the control construct. Taken together, t hese results indicate that the IGF-IR can play a critical role in the progr ession of breast cancer. Our studies provide a basis for the development of future treatment strategies targeting the]GF-IR in metastatic breast cance r.