Regulation of breast cancer growth by insulin-like growth factors

C. Kent Osborne, David R. Clemmons, Carlos L. Arteaga

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The IGFs may be important autocrine, paracrine or endocrine growth factors for human breast cancer. IGF-I and II stimulate growth of cultured human breast cancer cells. IGF-I is slightly more potent, paralleling its higher affinity for the IGF-I receptor. Antibody blockade of the IGF-I receptor inhibits growth stimulation induced by both IGFs, suggesting that this receptor mediates the growth effects of both peptides. However, IGF-I receptor blockade does not inhibit estrogen (E2)-induced growth suggesting that secreted IGFs are not the major mediators of E2 action. Several breast cancer cell lines express IGF-II mRNA by both Northern analysis and RNase protection assay. IGF-II activity is found in conditioned medium by radioimmuno and radioreceptor assay, after removal of somatomedin binding proteins (BP) which are secreted in abundance. IGF-I is undetectable. BPs of ≅ 25 and 40 K predominate in ER-negative cell lines while BPs of 36 K predominate in ER-positive cells. Blockade of the IGF-I receptor inhibits anchorage-independent and monolayer growth in serum of a panel of breast cancer cell lines. Growth of one line (MDA-231) was also inhibited in vivo by receptor antibody treatment of nude mice. The antibody had no effect on growth of MCF-7 tumors. These data suggest the IGFs are important regulators of breast cancer cell proliferation and that antagonism of this pathway may offer a new treatment strategy.

Original languageEnglish (US)
Pages (from-to)805-809
Number of pages5
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume37
Issue number6
DOIs
StatePublished - Dec 20 1990

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Somatomedins
IGF Type 1 Receptor
Breast Neoplasms
Cells
Growth
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Cell Line
Antibodies
Assays
Insulin-Like Growth Factor Binding Proteins
Radioligand Assay
Cell proliferation
Ribonucleases
Conditioned Culture Medium
Nude Mice
Tumors
Monolayers
Intercellular Signaling Peptides and Proteins
Estrogens

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Regulation of breast cancer growth by insulin-like growth factors. / Kent Osborne, C.; Clemmons, David R.; Arteaga, Carlos L.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 37, No. 6, 20.12.1990, p. 805-809.

Research output: Contribution to journalArticle

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