Insulin-like growth factor-II overexpression in MCF-7 cells induces phenotypic changes associated with malignant progression

Kevin J. Cullen, Marc E. Lippman, David Chow, Suzanne Hill, Neal Rosen, James A. Zwiebel

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

It has been proposed that the insulin-like growth factors (IGFs) can act as autocrine and/or paracrine growth promoters in breast cancer. To investigate this hypothesis, we infected early passage MCF-7 cells with a retroviral vector containing the coding sequence for the IGF-II preprohormone along with a constitutive cytomegalovirus promoter sequence. These cells do not normally express IGF-I or IGF-II. After infection with the retroviral vector, several single cell clones were analyzed. Seven of nine isolated clones expressed very high levels of IGF-II mRNA. Biologically active IGF-II protein was easily detectable in the medium conditioned by the IGF-II-expressing clones, and IGF receptors were down-regulated in these. All IGF-II-expressing clones showed marked morphological changes in anchorage-dependent culture, growing in large clumps and as free-floating colonies. The cells also cloned in soft agar in the absence of estrogen, while the wild-type MCF-7 cells and control cells infected with an irrelevant DNA sequence showed none of these properties. αIR-3, an antibody that blocks the type I IGF receptor, inhibited the growth of IGF-II-expressing clones in serum-free medium. This model demonstrates that IGF-II can serve as an autocrine growth stimulant in breast cancer epithelial cells and that IGF-II overexpression may be capable of mediating malignant progression in human breast cancer.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalMolecular Endocrinology
Volume6
Issue number1
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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