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

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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
Volume6
Issue number3
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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