Integrin α6Bβ4 inhibits colon cancer cell proliferation and c-Myc activityReport as inadecuate




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BMC Cancer

, 9:223

First Online: 09 July 2009Received: 27 January 2009Accepted: 09 July 2009DOI: 10.1186-1471-2407-9-223

Cite this article as: Dydensborg, A.B., Teller, I.C., Groulx, JF. et al. BMC Cancer 2009 9: 223. doi:10.1186-1471-2407-9-223

Abstract

BackgroundIntegrins are known to be important contributors to cancer progression. We have previously shown that the integrin β4 subunit is up-regulated in primary colon cancer. Its partner, the integrin α6 subunit, exists as two different mRNA splice variants, α6A and α6B, that differ in their cytoplasmic domains but evidence for distinct biological functions of these α6 splice variants is still lacking.

MethodsIn this work, we first analyzed the expression of integrin α6A and α6B at the protein and transcript levels in normal human colonic cells as well as colorectal adenocarcinoma cells from both primary tumors and established cell lines. Then, using forced expression experiments, we investigated the effect of α6A and α6B on the regulation of cell proliferation in a colon cancer cell line.

ResultsUsing variant-specific antibodies, we observed that α6A and α6B are differentially expressed both within the normal adult colonic epithelium and between normal and diseased colonic tissues. Proliferative cells located in the lower half of the glands were found to predominantly express α6A, while the differentiated and quiescent colonocytes in the upper half of the glands and surface epithelium expressed α6B. A relative decrease of α6B expression was also identified in primary colon tumors and adenocarcinoma cell lines suggesting that the α6A-α6B ratios may be linked to the proliferative status of colonic cells. Additional studies in colon cancer cells showed that experimentally restoring the α6A-α6B balance in favor of α6B caused a decrease in cellular S-phase entry and repressed the activity of c-Myc.

ConclusionThe findings that the α6Bβ4 integrin is expressed in quiescent normal colonic cells and is significantly down-regulated in colon cancer cells relative to its α6Aβ4 counterpart are consistent with the anti-proliferative influence and inhibitory effect on c-Myc activity identified for this α6Bβ4 integrin. Taken together, these findings point out the importance of integrin variant expression in colon cancer cell biology.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-223 contains supplementary material, which is available to authorized users.

Anders Bondo Dydensborg, Inga C Teller contributed equally to this work.

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Author: Anders Bondo Dydensborg - Inga C Teller - Jean-François Groulx - Nuria Basora - Fréderic Paré - Elizabeth Herring - Ré

Source: https://link.springer.com/







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