Effect of overexpression of very low density lipoprotein receptor on cell growth.

The very low density lipoprotein (VLDL) receptor is a member of the LDL receptor gene family and binds only apoE-containing lipoproteins. Although the VLDL receptor has been shown to play an important role in the proliferation of vascular smooth muscle cells and the formation of foam cells as primary responses of atherogenesis, its actual functions are still unclear. To understand the biological roles of the VLDL receptor in foam cell formation and cell growth, we tried to overexpress VLDL receptors in various cells. When COS-7 cells were transfected with an expression plasmid containing VLDL receptor cDNA, cell growth was inhibited by overexpression of the receptor and this growth inhibition was ligand-independent. The O-linked glycosylation region, but not the cytoplasmic domain, of the receptor appeared to be responsible for this growth inhibition. On the other hand, VLDL receptor expression induced enhanced incorporation of lipids and cytoplasmic enlargement. These changes were dependent on the exogenous ligand and the cytoplasmic domain of the receptor. These results suggest that the VLDL receptor functions as a regulator of cell growth and differentiation, which may be distinct from its lipid-incorporating function.