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 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 Tuna, Hiroaki Itamochi
• Journal: Tumori (Tumori) 2013 Nov-Dec Vol. 99 Issue 6 Pg. 715-22 ISSN: 2038-2529 [Electronic] United States
• PMID: 24503796 (Publication Type: Journal Article)

Chemical References

• RNA Isoforms
• RNA, Messenger
• RNA, Neoplasm
• WT1 Proteins
• WT1 protein, human
• Insulin-Like Growth Factor I
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Blotting, Western
• Breast Neoplasms (genetics, metabolism, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Wilms Tumor
• Humans
• Insulin-Like Growth Factor I (metabolism)
• MCF-7 Cells (metabolism)
• Neoplasm Staging
• Predictive Value of Tests
• Prognosis
• RNA Isoforms (metabolism)
• RNA Processing, Post-Transcriptional
• RNA, Messenger (metabolism)
• RNA, Neoplasm (metabolism)
• Receptor, ErbB-2 (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation
• WT1 Proteins (genetics)