Inhibition of cell proliferation by apolipoprotein E isoform expression.
The anti-atherogenic effects of human apolipoprotein E3 (apoE3) have been partially attributed to its anti-proliferation properties. We studied if endogenously expressed apoE elicits isoform-dependent effects on cell proliferation. Rat F111 fibroblasts without native expression of apoE were used to establish cell lines with stable expression of the three human apoE isoforms. Cell growth curve studies showed that expression of apoE isoforms prolonged cell population doubling time in an isoform-dependent manner with apoE3 showing the most potent effect followed by apoE2 and apoE4 exhibiting comparable effects. Interestingly, saturation density of cell population was significantly reduced by the expression of apoE4 isofom. Further analyses revealed that all three apoE isoforms significantly lengthened G0/G1 phase (p < 0.05) of the cell cycle and were associated with the suppression of ERK1/2 activities. However, these changes were not sufficient to explain the isoform-dependent effects of apoE expression on cell population doubling time and saturation density.
Chan
Wing-Man
WM
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Ho
Yuan-Yuan
YY
D000818:Animals; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media / Q000032:analysis / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D003470:Culture Media; D006131:Growth Inhibitors; D011994:Recombinant Proteins