Email updates

Keep up to date with the latest news and content from BMC Molecular Biology and BioMed Central.

Open Access Research article

L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions

Marco Pfeifer1, Uwe Schirmer1, Claudia Geismann2, Heiner Schäfer2, Susanne Sebens2 and Peter Altevogt1*

Author Affiliations

1 German Cancer Research Center, Department of Translational Immunology, D015, D-69120 Heidelberg, Germany

2 Clinic for Internal Medicine I, Laboratory of Molecular Gastroenterology and Hepatology, UKSH-Campus, University of Kiel, D- 21405 Kiel, Germany

For all author emails, please log on.

BMC Molecular Biology 2010, 11:64  doi:10.1186/1471-2199-11-64

Published: 27 August 2010

Abstract

Background

The L1 cell adhesion molecule (L1CAM) was originally identified as a neural adhesion molecule involved in axon guidance. In many human epithelial carcinomas L1CAM is overexpressed and thereby augments cell motility, invasion and metastasis formation. L1CAM positive carcinomas are associated with bad prognosis. Recent data point out that L1CAM is regulated in a fashion similar to epithelial-mesenchymal transition (EMT). Previous studies have implied the transcription factors Slug and/or β-catenin in L1CAM transcriptional regulation. However, the regulation of human L1CAM expression at the transcriptional level is not well understood.

Results

To better understand the molecular basis of L1CAM transcriptional regulation, we carried out a detailed characterization of the human L1CAM promoter. We identified two transcription start sites, the first in front of a non-translated exon 0 (promoter 1) and the other next to the first protein-coding exon 1 (promoter 2). Both sites could be verified in endometrial carcinoma (EC) cell lines and appear to be used in a cell-type specific manner. The two identified promoter regions showed activity in luciferase reporter assays. Chromatin-IP analyses confirmed the in silico predicted E-boxes, binding sites for transcription factors Snail and Slug, as well as Lef-1 sites, which are related to β-catenin-mediated transcriptional regulation, in both promoters. Overexpression of β-catenin exclusively augmented activity of promoter 1 whereas Slug enhanced promoter 1 and 2 activity suggesting that both promoters can be active. Overexpression of β-catenin or Slug could upregulate L1CAM expression in a cell-type specific manner.

Conclusions

Our results, for the first time, provide evidence that the L1CAM gene has two functionally active promoter sites that are used in a cell-type specific manner. Slug and β-catenin are involved L1CAM transcriptional regulation. Nevertheless, Slug rather than β-catenin levels are correlated with L1CAM expression in EC cell lines. Our findings suggest that the L1CAM transcriptional regulation is more complex than anticipated and this study provides the basis for a better understanding of L1CAM regulation in non-neuronal/tumor cells.