Role of cyclic AMP response element-binding protein in insulin-like growth factor-i receptor up-regulation by sex steroids in prostate cancer cells.

Abstract

Insulin-like growth factor-I receptor (IGF-IR) overexpression may play a role in prostate cancer progression. We found previously that, in prostate cancer cells, IGF-IR is up-regulated by both androgens and estrogens via a nongenotropic pathway. We now show that, in prostate cancer cells, stimulation with either androgens or estrogens up-regulates IGF-IR by inducing cyclic AMP response element-binding protein (CREB) activation. Both sex steroids phosphorylated CREB at Ser(133) in a dose-dependent manner in androgen receptor (AR)-positive LNCaP cells, whereas only estrogens phosphorylated CREB in AR-negative PC3 cells. CREB phosphorylation involved c-Src-dependent extracellular signal-regulated kinase 1/2 activation, but not protein kinase A, protein kinase C, or calmodulin-dependent kinase II, and occurred also in cells transfected with AR or estrogen receptor mutants that do not localize into the nucleus. CREB silencing abrogated IGF-IR up-regulation and promoter activation. We also showed that CREB binds to IGF-IR promoter region and identified the relevant CREB-binding site at the 5'-untranslated region fragment of IGF-IR promoter. In conclusion, we describe a novel mechanism of IGF-IR up-regulation and promoter activity by CREB activation, induced by sex steroids, through a nongenotropic signaling.

DOI: 10.1158/0008-5472.CAN-09-0088

6 Figures and Tables

01002002011201220132014201520162017
Citations per Year

276 Citations

Semantic Scholar estimates that this publication has 276 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Genua2009RoleOC, title={Role of cyclic AMP response element-binding protein in insulin-like growth factor-i receptor up-regulation by sex steroids in prostate cancer cells.}, author={M Isabel Genua and G Pandini and Diego Sisci and Gabriella Castoria and Marcello Maggiolini and Riccardo Vigneri and Antonino Belfiore}, journal={Cancer research}, year={2009}, volume={69 18}, pages={7270-7} }