Insulin-like growth factor-II (IGF-II): A potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor

C. Kent Osborne, Ester B. Coronado, Libbey J. Kitten, Carlos L. Arteaga, Suzanne A.W. Fuqua, K. Ramasharma, Milton Marshall, Choh Hao Lit

Research output: Contribution to journalArticle

244 Scopus citations

Abstract

Insulin-like growth factor-ll (IGF-II) is a potent mitogen for several types of cultured cells and tissues. We have studied the interaction of IGF-II with a panel of cultured human breast cancer cell lines, examining the possibility that these cells synthesize and secrete IGF-II activity which could have autocrine/ paracrine functions. Synthetic IGF-II was mitogenic in five of seven cell lines tested, including the estrogen receptor-positive lines MCF-7L, ZR75-1, and T47D and the estrogen receptor (ER)-negative lines Hs578T and MDA-231. IGF-II was slightly less potent than IGF-I in stimulating DNA synthesis in MCF-7I cells, an effect that paralleled its ability to compete for [125I]IGF-I binding in these cells. Affinity labeling studies revealed that IGF-II could also compete for binding to the 130,000 mol wt α-subunit of the IGF-I receptor. A monoclonal antibody to the IGF-I receptor inhibited the mitogenic effects of IGF-II in MCF-7L and MDA-231 cells, suggesting that this receptor mediates the growth effects of IGF-II in these breast cancer cells. Using a RIA and a RRA, IGF-ll-like activity was detected in conditioned medium extracts processed to remove IGF-binding proteins from several breast cancer cell lines, with the highest levels found in conditioned medium from MCF-7L and T47D cell lines. IGF-II mRNA transcripts in MCF-7L and T47D cells were identified by Northern blot analysis and were confirmed by RNase protection assay. IGF-II mRNA was increased by estrogen in MCF-7L cells. These data suggest that IGF-II is an important mitogen for certain breast cancer cells and that its effects are mediated via the IGF-I receptor. The ability of these cells to express IGF-II mRNA and secrete IGF-II activity into the culture medium further supports the hypothesis that IGF-II may have autocrine/paracrine as well as endocrine growth regulatory functions in human breast cancer.

Original languageEnglish (US)
Pages (from-to)1701-1709
Number of pages9
JournalMolecular Endocrinology
Volume3
Issue number11
DOIs
StatePublished - Nov 1989

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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