Apolipoprotein E inhibits serum-stimulated cell proliferation and enhancesserum-independent cell proliferation

Independently of its role in lipid homeostasis, apolipoprotein E (apoE) inh ibits cell proliferation. We compared the effects of apoE added to media (e xogenous apoE) with the effects of stably expressed apoE (endogenous apoE) on cell proliferation. Exogenous and endogenous apoE increased population d oubling times by 30-50% over a period of 14 days by prolonging the G(1) pha se of the cell cycle. Exogenous and endogenous apoE also decreased serum-st imulated DNA synthesis by 30-50%. However, apoE did not cause cell cycle ar rest; both apoE-treated and control cells achieved equivalent saturation de nsities at 14 days. Further analyses demonstrated that exogenous and endoge nous apoE prevented activation of MAPK but not induction of c-fos expressio n in response to serum growth factors. Endogenous (but not exogenous) apoE altered serum concentration-dependent effects on proliferation. Whereas con trol (non-apoE-expressing) cell numbers increased with increasing serum con centrations (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 synt hesis levels compared with control cells. We conclude that apoE does not si mply inhibit cell proliferation; rather, the presence of apoE alters the re sponse to and requirement for serum mitogens.