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

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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 - Jan 1 1989

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IGF Type 1 Receptor
Insulin-Like Growth Factor II
Intercellular Signaling Peptides and Proteins
Breast Neoplasms
Cell Line
Conditioned Culture Medium
Insulin-Like Growth Factor I
Mitogens
Estrogen Receptors
Messenger RNA
Insulin-Like Growth Factor Binding Proteins
Somatomedins
Ribonucleases
Growth
Northern Blotting
Culture Media

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Insulin-like growth factor-II (IGF-II) : A potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor. / Osborne, C. Kent; Coronado, Ester B.; Kitten, Libbey J.; Arteaga, Carlos L.; Fuqua, Suzanne A.W.; Ramasharma, K.; Marshall, Milton; Lit, Choh Hao.

In: Molecular Endocrinology, Vol. 3, No. 11, 01.01.1989, p. 1701-1709.

Research output: Contribution to journalArticle

Osborne, C. Kent ; Coronado, Ester B. ; Kitten, Libbey J. ; Arteaga, Carlos L. ; Fuqua, Suzanne A.W. ; Ramasharma, K. ; Marshall, Milton ; Lit, Choh Hao. / Insulin-like growth factor-II (IGF-II) : A potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor. In: Molecular Endocrinology. 1989 ; Vol. 3, No. 11. pp. 1701-1709.
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