Antisense-mediated reduction in insulin-like growth factor-I receptor expression suppresses the malignant phenotype of a human alveolar rhabdomyosarcoma

David N. Shapiro, Bart G. Jones, Linda H. Shapiro, Peter Dias, Peter J Houghton

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

The expression of the insulin-like growth factors (IGFs) and their receptors has been linked to cellular proliferation and tumorigenicity in a number of model systems. Since rhabdomyosarcoma cells express IGF-I receptors, an autocrine or paracrine loop involving this receptor and its ligands could be responsible in part for the growth characteristics of this tumor. To assess directly the role of the IGF-I receptor in rhabdomyosarcoma cell growth and tumorigenicity, a human alveolar rhabdomyosarcoma cell line with high IGF-I receptor expression was transfected with an amplifiable IGF- I receptor antisense expression vector. Four unique, transfected clones were analyzed and found to have reduced IGF-I receptor expression relative to the parental line. Integration of the antisense sequence was demonstrated by Southern blot analysis, and expression of antisense message in these clones was shown by S1 nuclease protection assay. Reduced IGF-I receptor surface expression in the transfectants was shown by decreased immunofluorescence with an IGF-I receptor monoclonal antibody and by decreased IGF-I binding as measured by Scatchard analysis. These clones had markedly reduced growth rates in vitro, impaired colony formation in soft agar, and failed to form tumors in immunodeficient mice when compared with vector-transfected clones. These results demonstrate that reduction of IGF-I receptor expression can inhibit both the in vitro and in vivo growth of a human rhabdomyosarcoma cell line and suggest a role for the IGF-I receptor in mediating neoplastic growth in this mesenchymally derived tumor.

Original languageEnglish (US)
Pages (from-to)1235-1242
Number of pages8
JournalJournal of Clinical Investigation
Volume94
Issue number3
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Alveolar Rhabdomyosarcoma
IGF Type 1 Receptor
Phenotype
Rhabdomyosarcoma
Clone Cells
Growth
Nuclease Protection Assays
Somatomedin Receptors
Alveolar Epithelial Cells
Cell Line
Neoplasms
Southern Blotting
Insulin-Like Growth Factor I
Agar
Fluorescent Antibody Technique
Monoclonal Antibodies
Cell Proliferation
Ligands

Keywords

  • antisense RNA
  • autocrine
  • downregulation
  • insulin-like growth factor receptor
  • paracrine

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Antisense-mediated reduction in insulin-like growth factor-I receptor expression suppresses the malignant phenotype of a human alveolar rhabdomyosarcoma. / Shapiro, David N.; Jones, Bart G.; Shapiro, Linda H.; Dias, Peter; Houghton, Peter J.

In: Journal of Clinical Investigation, Vol. 94, No. 3, 01.01.1994, p. 1235-1242.

Research output: Contribution to journalArticle

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