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Originally published In Press as doi:10.1074/jbc.M104735200 on July 26, 2001

J. Biol. Chem., Vol. 276, Issue 41, 37815-37820, October 12, 2001
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Expression of p21Waf1/Cip1 and Cyclin D1 Is Increased in Butyrate-resistant HeLa Cells*

Anna DerjugaDagger , Christina Richard§, Milena CrosatoDagger , Paul S. Wright, Lorraine ChalifourDagger , Joe Valdez||, Anna Barraso||, Harry A. Crissman||, Walter Nishioka**, E. Morton Bradbury||, and John P. H. Th'ng§Dagger Dagger

From the Dagger  Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada,  Aventis Pharmaceutical Inc., Bridgewater, New Jersey 08807, || Los Alamos National Laboratories, New Mexico 87545, ** Vical Inc., San Diego, California 92121, and § Northwestern Ontario Regional Cancer Center, Thunder Bay, Ontario P7A 7T1, Canada

Sodium butyrate induced cell cycle arrest in mammalian cells through an increase in p21Waf1/Cip1, although another study showed that this arrest is related to pRB signaling. We isolated variants of HeLa cells adapted to growth in 5 mM butyrate. One of these variants, clone 5.1, constitutively expressed elevated levels of p21Waf1/Cip1 when incubated in regular growth medium and in the presence of butyrate. Despite this elevated level of p21Waf1/Cip1, the cells continue to proliferate, albeit at a slower rate than parental HeLa cells. Western blot analyses showed that other cell cycle regulatory proteins were not up-regulated to compensate for the elevated expression of p21Waf1/Cip1. However, cyclin D1 was down-regulated by butyrate in HeLa cells but not in clone 5.1. We conclude that continued expression of cyclin D1 allowed clone 5.1 to grow in the presence of butyrate and elevated levels of p21Waf1/Cip1.


* This work was supported by a grant from the Medical Research Council of Canada (to J. T.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Dagger To whom correspondence should be sent: Northwestern Ontario Regional Cancer Centre, 290 Munro St., Thunder Bay, Ontario P7A 7T1 Canada; Tel.: 807-343-1542; Fax: 807-343-1549; E-mail: john.th'ng@cancercare.on.ca.


Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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