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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
Expression of p21Waf1/Cip1 and Cyclin D1 Is Increased
in Butyrate-resistant HeLa Cells*
Anna
Derjuga ,
Christina
Richard§,
Milena
Crosato ,
Paul S.
Wright¶,
Lorraine
Chalifour ,
Joe
Valdez ,
Anna
Barraso ,
Harry A.
Crissman ,
Walter
Nishioka**,
E. Morton
Bradbury , and
John P. H.
Th'ng§
From the 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.

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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