Growth inhibition of mcf-7 breast cancer cells by stable expression of an insulin-like growth factor i receptor antisense ribonucleic acid

Stefan Neuenschwander, Charles T. Roberts, Derek Leroith

    Research output: Contribution to journalArticle

    129 Scopus citations

    Abstract

    Insulin-like growth factors (IGFs) play an important role in cellular proliferation, and IGF action appears to be involved in tumorigenesis. To determine the role of the IGF-I receptor in breast cancer cell growth, we stably transfected MCF-7 breast cancer cells with a construct encoding an antisense RNA complementary to the region surrounding the translation initiation site of the IGF-I receptor messenger RNA (mRNA). Control cells were transfected with vector alone. Clones expressing the antisense RNA exhibited a 30% reduction in endogenous IGF-I receptor mRNA levels and a significant reduction in receptor protein levels, as measured by both ligand binding assays and Western blot analysis. Antisense-expressing clones expressed approximately 30,000 receptors/cell compared with approximately 48,000-58,000 receptors/cell in control (neo) cells (P < 0.05). Although endogenous RNA:RNA hybrids were demonstrable in antisense-expressing cells, our results suggest that the major effect of the antisense may be the reduction in mRNA levels and not via an inhibition of translation. The reduction in receptor expression reduced both IGF-I- and serum-stimulated cellular proliferation. The maximum cell number reached at 96 h in the presence of IGF-I (100 ng/ml) was significantly reduced in antisense-expressing clones (22,000-30,000) compared with that in control (neo) cells (39,000-42,000). Furthermore, IGF-I-induced c-fos gene expression was reduced by 30% in the clones expressing the antisense RNA. These results strongly support a role for the IGF-I receptor in the proliferation of human breast cancer cells and suggest that strategies using this type of technology may prove useful in cancer therapy.

    Original languageEnglish (US)
    Pages (from-to)4298-4303
    Number of pages6
    JournalEndocrinology
    Volume136
    Issue number10
    DOIs
    StatePublished - Oct 1995

    ASJC Scopus subject areas

    • Endocrinology

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