The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability

la Cour, Jonas M.; Høj, Berit R.; Mollerup, Jens; Simon, Ronald; Sauter, Guido; Berchtold, Martin W.

doi:10.1016/j.molonc.2007.08.002

« Previous Next »Molecular Oncology
Volume 1, Issue 4 , Pages 431-439, April 2008

The apoptosis linked gene ALG-2 is dysregulated in tumors of various origin and contributes to cancer cell viability

Jonas M. la Cour
- Copenhagen Biocenter, Department of Molecular Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark
Berit R. Høj
- Copenhagen Biocenter, Department of Molecular Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark
Jens Mollerup
- Copenhagen Biocenter, Department of Molecular Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark
Ronald Simon
- Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Guido Sauter
- Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Martin W. Berchtold
- Copenhagen Biocenter, Department of Molecular Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark
- Corresponding author. Tel.: +45 35322089; fax: +45 35322128.

Received 26 June 2007; received in revised form 14 August 2007; accepted 14 August 2007. published online 10 September 2007.

Abstract

The apoptosis linked gene-2 (ALG-2), discovered as a proapoptotic calcium binding protein, has recently been found upregulated in lung cancer tissue indicating that this protein may play a role in the pathology of cancer cells and/or may be a tumor marker. Using immunohistochemistry on tissue microarrays we analysed the expression of ALG-2 in 7371 tumor tissue samples of various origin as well as in 749 normal tissue samples. Most notably, ALG-2 was upregulated in mesenchymal tumors. No correlation was found between ALG-2 staining intensity and survival of patients with lung, breast or colon cancer. siRNA mediated ALG-2 downregulation led to a significant reduction in viability of HeLa cells indicating that ALG-2 may contribute to tumor development and expansion.

Keywords: Calcium binding proteins, Tissue microarray, Gene silencing, ALG-2

Abbreviations: ALG-2, apoptosis linked gene-2, TMA, tissue microarray, MTA, multitumor array, NTA, normal tissue array, PEF, penta EF-hand proteins, SDS, sodium dodecyl sulfate, DTT, dithiothreitol, SDS-PAGE, SDS-polyacrylamide gel electrophoresis, PVDF, polyvinyl difluoride, GIST, gastrointestinal tumors, DCIS, ductal carcinomas in situ, PNET, pancreatic neuroendocrine tumor, 7AAD, 7-amino-actinomycin D, SEM, standard error of the mean