Insulin-like growth factor I regulates the expression of isoforms of Wilms' tumor 1 gene in breast cancer

Abstract

Aim and background The Wilms' tumor 1 gene (WT1) is overexpressed in many cancers, including breast cancer, and its high expression is an adverse prognostic factor. However, the factors that regulate WT1 expression are poorly understood. Methods and study design Expression of genes at the RNA and protein level was detected by reverse transcriptase-polymerase chain reaction, western blotting, and reverse-phase protein array assays in breast cancer cell lines and tumor samples. Results In the study, we showed that the treatment of MCF-7 breast cancer cells with insulin-like growth factor I (IGF-I) increases WT1 protein expression by 77%. IGF-I uses Akt to up-regulate WT1 expression. Conversely, inhibition of IGF-I by IGF-binding protein 3 and of IGF-I receptor (IGF-IR) by anti-IGF-IR antibody (α-IR3) uses Akt to decrease WT1 protein levels in MCF-7 cells. We thus newly identified a mechanism by which IGF-I up-regulates WT1, especially the (+exon 5/-KTS) isoform, at the post-transcriptional level in MCF-7 cells and primary breast tumor samples. Conclusions The results indicate a novel posttranscriptional regulatory factor of WT1 in MCF-7 breast cancer cells.