Insulin-like growth factor binding protein-3 is secreted as a phosphoprotein by human breast cancer cells

Scott T. Pattison, Susan Fanayan, Janet L. Martin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The growth regulatory activity of the insulin-like growth factor binding proteins (IGFBPs) may be modulated by post-translational modifications such as glycosylation, limited proteolysis and phosphorylation. In this study, we have examined phosphorylation of IGFBP-3 in two breast cancer cell lines: the estrogen receptor negative (ER(-ve)) Hs578T cell line in which IGFBP-3 is normally expressed, and ER(+ve) T47D breast cancer cells transfected with IGFBP-3 cDNA (T47D(BP-3)) and therefore expressing IGFBP-3 constitutively. Metabolic labelling with [32P] orthophosphate revealed that both cell lines secreted phosphorylated IGFBP-3 similar in size to plasma IGFBP-3 phosphorylated in vitro with casein kinase II, and that IGFBP-3 phosphorylation was differentially modulated in the two cell lines. In Hs578T cells, retinoic acid (10-100 nM) increased IGFBP-3 phosphorylation to a maximum of 150% of control. IGF-I, but not [LR3]IGF-I, reduced the proportion of phosphorylated IGFBP-3 in Hs578T conditioned medium, consistent with increased release of non-phosphorylated, cell-associated IGFBP-3. By contrast, IGFBP-3 phosphorylation in T47D(BP-3) cells was not affected by retinoic acid or IGF-I, but appeared slightly increased by estradiol. Together these data indicate that phosphorylation of IGFBP-3 in breast cancer cells may be regulated by agents known to affect breast cancer cell proliferation. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume156
Issue number1-2
DOIs
Publication statusPublished - 25 Oct 1999

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