Abstract
The integrin β4 subunit has been shown to be involved in various aspects of cancer progression. The aim of the present work was to evaluate the expression of β4 in primary colon cancers and to investigate the occurrence of a previously identified intestinal nonfunctional variant of β4 (β4ctd−) for adhesion to laminin. Immunodetection of β4 using a panel of antibodies and RT–PCR analyses were performed on series of paired primary colon tumors and corresponding resection margins. The β4 subunit was found to be significantly overexpressed in cancer specimens at both the protein and transcript levels. Surprisingly, β4 levels of expression were closely correlated with those of the oncogene c-Myc in individual specimens. In vitro studies of c-Myc overexpression showed an upregulation of β4 promoter activity. Finally, the β4ctd− form was identified in the normal proliferative colonic cells but was found to be predominantly absent in colon cancer cells, both in situ and in vitro. We concluded that the β4ctd− form is lost from colon cancer cells, while the level of the wild-type form of β4, which is functional for adhesion to laminin, is increased in primary tumors in relation with the expression of c-Myc.
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Acknowledgements
We thank Dr E Ruoslahti (The Burnham Institute, La Jolla, CA, USA), Dr J Bartek (Danish Cancer Society, Copenhagen, Denmark) and Drs T Yamada and S Hirohashi (National Cancer Center Research Institute, Tokyo, Japan) for generous gift of reagents, Drs Jean Gosselin, Michel Lessard (Département de Pathologie, Centre Hospitalier Universitaire de Sherbrooke) and Jacques Poisson (Département de chirurgie, Centre Hospitalier Universitaire de Sherbrooke) for their excellent cooperation in providing matched colon cancer specimens and pathological expertise and Dr Pierre Lavigne (Département de pharmacologie, Université de Sherbrooke). We also acknowledge the collaboration of the Cooperative Human Tissue Network, funded by the National Cancer Institute, in obtaining additional sets of matched colon cancer specimens. This work was supported by Grant MOP-62914 (to JF Beaulieu) and Group Grant MGC-15186 from the Canadian Institutes for Health Research. JF Beaulieu is the recipient of a Canadian Research Chair in Intestinal Physiopathology. N Basora and PH Vachon are ‘Chercheurs-boursiers’ of the Fonds de la recherche en santé du Québec; AB Dydensborg is supported by a studentship from the Danish Research Agency (642-02-0055).
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Ni, H., Dydensborg, A., Herring, F. et al. Upregulation of a functional form of the β4 integrin subunit in colorectal cancers correlates with c-Myc expression. Oncogene 24, 6820–6829 (2005). https://doi.org/10.1038/sj.onc.1208848
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DOI: https://doi.org/10.1038/sj.onc.1208848
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