Format

Send to

Choose Destination
See comment in PubMed Commons below
Mol Cancer. 2010 Mar 19;9:64. doi: 10.1186/1476-4598-9-64.

Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer.

Author information

1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.

Abstract

BACKGROUND:

Many cancerous cells accumulate beta-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of beta-catenin in the nuclei of oral cancer cells.

RESULTS:

We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of beta-catenin and GSK-3beta, association of beta-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, beta-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of beta-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation of beta-catenin (tyrosine) and GSK-3beta(Ser-(9), resulting in a loss of beta-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates beta-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of beta-catenin in oral cancer.

CONCLUSIONS:

EGFR signaling regulates beta-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of beta-catenin under EGFR activation is a malignancy marker of oral cancer.

PMID:
20302655
PMCID:
PMC2850885
DOI:
10.1186/1476-4598-9-64
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Support Center