HOME

Return to Table of Contents

28

THE INTEGRIN a6 SUBUNIT IS UPREGULATED IN ADENOCARCINOMAS OF THE HUMAN COLON AND UNDERGOES ALTERNATIVE SPLICING REMINISCENT OF THAT FOUND IN THE CRYPT OF THE NORMAL INTESTINE

AB Dydensborg, E Herring, J Auclair, J-F Beaulieu
CIHR Group in Functional Development and Physiopathology of the Digestive Tract, Département d'anatomie et de biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Quebec

BACKGROUND AND AIMS: Integrins are heterodimeric adhesion molecules that function as signalization platforms mediating signals of importance for cell cycle progression and survival as well as providing anchorage for the cell to the extracellular matrix. The integrin a6 subunit undergoes alternative splicing generating two variants: A and B, of which only the A variant appears to be capable of stimulating the Ras-MAP-kinase pathway of proliferation. We have previously demonstrated that the principal dimerization partner of the integrin a6 subunit, the b4 subunit, is upregulated in human colon carcinomas. We therefore investigated the expression pattern of the two splice-variants of the a6 integrin in normal intestinal tissue as well as in primary carcinomas of the human colon and adenocarcinoma cell lines.
METHODS: The expression pattern of the a6 variants in the adult intestine was determined by indirect immunofluorescence, while RT-PCR and Western blotting were used to delineate the expression pattern in intestinal cell lines. Quantitative real-time RT-PCR was used to determine the expression level of the a6 subunit in patient matched primary tumours and their corresponding normal resection margins.
RESULTS: Immunolocalization studies in the normal adult intestine showed a predominant expression of the a6A subunit in the proliferative cells of the crypt. Predominance of the a6A subunit in proliferative cells was also noted in the various intestinal cell lines tested while the expression the a6B variant was found to be relatively ubiquitous. In colon cancers, an overall upregulation of the expression of the a6 subunit was observed and was attributed to a specific upregulation of the a6A variant in primary tumours as compared with their corresponding normal resection margins in accordance with observations made in six colon cancer cells lines.
CONCLUSION: A close relation between the expression of the integrin a6A subunit and cell proliferation was observed in normal intestinal cells while in colon carcinoma cells, an increase in the a6A variant seems to account for the overall upregulation of the a6 subunit.
Supported by CIHR

PREVIOUS     NEXT