Cortisol regulates insulin-like growth-factor binding protein (igfbp) gene expression in Atlantic salmon parr

Glucose-6-phosphatase (G6Pase) and insulin-like growth factor-binding protein-1 (IGFBP-1) genes contain a homologous promoter sequence that is required for gene repression by insulin. Interestingly, this element interacts with members of the forkhead family of transcription factors [e.g. HNF3 (hepatic nuclear factor 3), FKHR (forkhead in rhabdomyosarcoma)] in vitro, while insulin promotes the phosphorylation and inactivation of FKHR in a phosphatidylinositol 3-kinase- and protein kinase B (PKB)-dependent manner. This mechanism has been proposed to underlie insulin action on G6Pase and IGFBP-1 gene transcription. However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase, but not IGFBP-1, gene expression. Indeed, phorbol ester treatment actually blocks the ability of insulin to repress IGFBP-1 gene expression. In addition, the action of phorbol esters is significantly reduced by inhibition of the p42/p44 mitogen-activated protein (MAP) kinase pathway. However insulin-induced phosphorylation of PKB or FKHR is not affected by the presence of phorbol esters. Therefore we suggest that activation of p42/p44 MAP kinases will reduce the sensitivity of the IGFBP-1 gene promoter, but not the G6Pase gene promoter, to insulin. Importantly, the activation of PKB and phosphorylation of FKHR is not, in itself, sufficient to reduce IGFBP-1 gene expression in the presence of phorbol esters.

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In Vivo Mechanical Loading Modulates Insulin-Like Growth Factor Binding Protein-2 Gene Expression in Rat Osteocytes

Calcified Tissue International ◽

10.1007/s00223-006-0077-4 ◽

2007 ◽

Vol 80 (2) ◽

pp. 137-143 ◽

Cited By ~ 24

Author(s):

C. M. A. Reijnders ◽

N. Bravenboer ◽

P. J. Holzmann ◽

F. Bhoelan ◽

M. A. Blankenstein ◽

...

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Mechanical Loading ◽

Binding Protein ◽

Insulin Like Growth Factor ◽

Factor Binding

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Transcriptional Activation of Insulin-Like Growth Factor-Binding Protein-4 by 17β-Estradiol in MCF-7 Cells: Role of Estrogen Receptor-Sp1 Complexes*

Endocrinology ◽

10.1210/endo.140.6.6751 ◽

1999 ◽

Vol 140 (6) ◽

pp. 2501-2508 ◽

Cited By ~ 37

Author(s):

Chunhua Qin ◽

Pomila Singh ◽

Stephen Safe

Keyword(s):

Gene Expression ◽

Estrogen Receptor ◽

Growth Factor ◽

Binding Protein ◽

Gene Promoter ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Human Estrogen Receptor ◽

17Β Estradiol ◽

Mcf 7

Abstract Insulin-like growth factor-binding protein-4 (IGFBP-4) is expressed in MCF-7 human breast cancer cells, and treatment of these cells with 17β-estradiol (E2) resulted in induction of IGFBP-4 gene expression (>3-fold) and protein secretion (>6-fold). To identify genomic sequences associated with E2 responsiveness, the 5′-promoter region (−1214 to +18) of the IGFBP-4 gene was cloned into a vector upstream from the firefly luciferase reporter gene, and E2 induced a 10-fold increase in luciferase activity in MCF-7 cells transiently transfected with this construct. Deletion analysis of this region of the IGFBP-4 gene promoter identified two GC-rich sequences at −559 to −553 and −72 to −64 that were important for E2-induced trans-activation. Gel mobility shift assays using 32P-labeled −569 to −540 and −83 to −54 oligonucleotides from the IGFBP-4 gene promoter showed that Sp1 protein bound these oligonucleotides to form a retarded band, and the intensity of the band was competitively decreased after coincubation with unlabeled IGFBP-4-derived and consensus Sp1 oligonucleotides. Mutation of the GC-rich sites within these sequences resulted in loss of the retarded band formation. Wild-type human estrogen receptor did not bind directly to the IGFBP-4 oligonucleotides; however, human estrogen receptor enhanced Sp1-DNA binding in a concentration-dependent manner. The results of this study demonstrate that at least two GC-rich sequences at −559 to −553 and− 72 to −64 are required for induction of IGFBP-4 gene expression by E2 in MCF-7 cells.

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