Differential regulation of insulin-like growth factor-binding protein-3 protease activity in MCF-7 breast cancer cells by estrogen and transforming growth factor-beta1.

Abstract:

:We have examined the regulation of an insulin-like growth factor-binding protein-3 (IGFBP-3) protease secreted by MCF-7 human breast cancer cells using a ligand-binding assay that relies on the decrease in affinity for des(1-3)IGF-I that occurs when IGFBP-3 becomes proteolyzed. IGFBP-3 protease activity was not altered by treatment of MCF-7 cells with all-trans-retinoic acid, vitamin D, epidermal growth factor, platelet-derived growth factor, insulin, or forskolin. However, estradiol was a potent stimulator of IGFBP-3 protease activity, with a significant and maximal effect at 1 nM. This was prevented by cotreatment with tamoxifen, which had no significant effect in the absence of estradiol. By contrast, TGFbeta1 dose dependently inhibited the amount of protease activity secreted by MCF-7 cells, with complete reversal of IGFBP-3 degradation apparent in response to 10 ng/ml TGFbeta1. This study has demonstrated that estrogens and TGFbeta1, factors that are stimulatory and inhibitory, respectively, for MCF-7 cell growth, also stimulate and inhibit the production of an enzyme capable of proteolyzing the growth inhibitory protein IGFBP-3.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Salahifar H,Baxter RC,Martin JL

doi

10.1210/endo.141.9.7684

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

3104-10

issue

9

eissn

0013-7227

issn

1945-7170

journal_volume

141

pub_type

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