Insulin-like growth factor II overexpression in myoblasts induces phenotypic changes typical of the malignant phenotype

C. P. Minniti, D. Luan, C. O'Grady, R. G. Rosenfeld, Y. Oh, L. J. Helman

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37 Scopus citations


The objective of this study was to examine the role of insulin-like growth factor II (IGF-II) in the pathogenesis of human rhabdomyosarcomas (RMS). We have demonstrated previously that RMS express high levels of IGF-II mRNA, secrete IGF-II peptide, and express both IGF-I and IGF-II receptors. Moreover, we showed that IGF-II functions as an autocrine growth and motility factor in RMS. Since IGF-II is expressed at high levels in fetal muscle cells and RMS are tumors thought to derive from skeletal myoblasts arrested along the normal myogenic pathway, autocrine production of IGF-II by RMS may be an etiological event in the development of this tumor. We have developed a model system which enabled us to study the effects of endogenous IGF-II overprotection in muscle myoblasts. Human cDNA for pre-prohormone IGF-II was transfected into mouse myoblasts in order to achieve high, constant expression of this growth factor, which is normally down-regulated at the end of the differentiation process. Expression of high IGF-II levels resulted in: (a) an increased proliferative rate; (b) impairment of the ability to differentiate into myoblasts; and (c) acquisition of the capability of anchorage-independent growth. No changes in the expression of IGF-I receptors were noted. We conclude that IGF-II overexpression in muscle myoblasts induces morphological and biological changes typical of the malignant phenotype and represents a fundamental event in the pathogenesis of RMS and possibly of other embryonal tumors.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalCell Growth and Differentiation
Issue number3
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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