Published online 11 March 2002. doi:10.1083/jcb1566rr1
© The Rockefeller University Press,
0021-9525/2002/3/940 $5.00
The Journal of Cell Biology, Volume 156, Number 6, March 18, 2002 940-940
Anticancer lubrication
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Mice lacking Muc2 develop colon tumors.
Velcich/AAAS
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Anew mouse model for the study of cancer reveals that mucus lubrication in the intestine is vital for preventing tumor formation.
Unregulated expression of Muc2, the most abundant mucin in the gastrointestinal lining, is often found in human tumors. Furthermore, the goblet cells that synthesize and secrete mucins are often depleted in intestinal mucosal structures that progress to tumors. These findings led Anna Velcich (Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY) and colleagues to examine the effects of Muc2 during the early steps of tumorigenesis.
Mice lacking Muc2 had an increased ratio of proliferating to apoptotic epithelial cells, resulting in altered maturation and increased migration of epithelial cells in the intestine. They were also more likely to develop intestinal, colon, and rectal tumors. The mice are the first good model for studying rectal tumors, which are common in humans.The exact pathway from lack of mucin to cancer is not known. c-Myc overexpression was present, but the nuclear accumulation of ß-catenin and the overt inflammatory response present in other mouse models were not found in the Muc2 mutants. Velcich speculates that Muc2 may shield cells from noxious molecules in the lumen content, such as bile acids, that may trigger cell proliferation.
Reference:
Velcich, A., et al. 2002. Science. 295:1726–1729.[Abstract/Free Full Text]
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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