title: Insulin-like growth factor I regulates the expression of isoforms of Wilms' tumor 1 gene in breast cancer.
abstract: OBJECTIVE
  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
  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 posttranscriptional 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.
authors: Musaffe
authors: M
authors: Tuna
authors: Hiroaki
authors: H
authors: Itamochi
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D061986:MCF-7 Cells / Q000378:metabolism; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D059368:RNA Isoforms / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D007334:Insulin-Like Growth Factor I; D059368:RNA Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D025721:WT1 Proteins; C583751:WT1 protein, human; C508053:ERBB2 protein, human