Non-receptor mediated, post-transcriptional regulation of insulinlike growth factor binding protein (IGFBP)-3 in Hs578T human breast cancer cells

Youngman Oh, Hermann L. Muller, Hung Pham, George Lamson, Ron G. Rosenfeld

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Hs578T human breast cancer cells secrete insulin-like growth factor binding protein 3 (IGFBP-3) as the major BP species. In addition, cell surface-associated IGFBP-3 is demonstrable by the use of cell monolayer affinity cross-linking or immunoperoxidase staining of the cell surface with a specific polyclonal anti-human IGFBP-3 antibody (αIGFBP-3γl). In this study, we have demonstrated that regulation ofHs578T IGFBP-3 by IGF peptides is specific, non-receptor mediated, and post-translational by showing: 1) dose-dependent increase of IGFBP-3 in conditioned media (CM) following addition of IGF-I and -II (maximum 13 fold increase at 100 ng/ml), but not by insulin up to 1 mg/ml; 2) no change in CM IGFBP-3 level by [Gln3, Ala4, Tyr15, Leu16]IGF-I, which has decreased affinity for IGFBPs; 3) no change in IGFBP-3 mRNA following addition of IGFs; 4) release of cell surface-associated IGFBP-3 into CM by the addition of IGFs, but not by [Gln3, Ala4, Tyr15, Leu16]IGF-I. These studies demonstrate that IGF peptides regulate CM concentrations of IGFBP-3 through nonreceptor mediated dissociation of cell surface-associated IGFBP-3.

Original languageEnglish (US)
Pages (from-to)3123-3125
Number of pages3
JournalEndocrinology
Volume131
Issue number6
DOIs
StatePublished - Dec 1992

ASJC Scopus subject areas

  • Endocrinology

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