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J. Biol. Chem., Vol. 276, Issue 46, 43455-43462, November 16, 2001
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From the Independently of its role in lipid homeostasis,
apolipoprotein E (apoE) inhibits cell proliferation. We compared the
effects of apoE added to media (exogenous apoE) with the effects of
stably expressed apoE (endogenous apoE) on cell proliferation.
Exogenous and endogenous apoE increased population doubling times by
30-50% over a period of 14 days by prolonging the
G1 phase of the cell cycle. Exogenous and endogenous
apoE also decreased serum-stimulated DNA synthesis by 30-50%.
However, apoE did not cause cell cycle arrest; both apoE-treated and
control cells achieved equivalent saturation densities at 14 days.
Further analyses demonstrated that exogenous and endogenous apoE
prevented activation of MAPK but not induction of c-fos
expression in response to serum growth factors. Endogenous (but not
exogenous) apoE altered serum concentration-dependent effects on proliferation. Whereas control (non-apoE-expressing) cell
numbers increased with increasing serum concentrations (1.6-fold for
every 2-fold increase in serum), apoE-expressing cell numbers did not
differ as serum levels were raised from 2.5 to 10%. In addition, in
low serum (0.1%), apoE-expressing cells had elevated DNA synthesis
levels compared with control cells. We conclude that apoE does not
simply inhibit cell proliferation; rather, the presence of apoE alters
the response to and requirement for serum mitogens.
Apolipoprotein E Inhibits Serum-stimulated Cell Proliferation and
Enhances Serum-independent Cell Proliferation*
§,¶,
,¶
Institute of Human Nutrition and the
¶ Department of Pediatrics, Columbia University, New York, New
York 10032 and ** Biotechnology General Limited,
Rehovot 76326, Israel
*
This work was supported by National Institutes of Health
Grants HL40404 and CA79737, National Livestock and Meat Board Grant 6-41809, an American Institute of Nutrition predoctoral fellowship (to
Y.-Y. H.), and American Cancer Society Grant RPG-95-024-03.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.
Present address: Dept. of Neuroscience, Johns Hopkins
University School of Medicine, PCTB 1004, 725 N. Wolfe St., Baltimore, MD 21205.
To whom correspondence should be addressed: Inst. of Human
Nutrition, Columbia University, HHSC 5-503, 701 W. 168th St., New York,
NY 10032. Tel.: 212-305-2107, Fax: 212-305-3079; E-mail: dat1@columbia.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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