EVIDENCE FOR UP-REGULATED LOW-DENSITY-LIPOPROTEIN RECEPTOR IN HUMAN LUNG ADENOCARCINOMA CELL LINE-A549

Human lung adenocarcinoma cell line A549 was studied with respect to t he metabolism of human low density lipoprotein (LDL) and 3-hydroxy-3-m ethyl-glutaryl-coenzyme A reductase (HMGR) activity. After incubation in medium containing lipoprotein-deficient serum (LPDS) for 24 h, the A549 cell line expresses a single class of high affinity LDL binding s ites (K(D) at 37-degrees-C of 15.1 +/- 0.7 nM and capacity of 118 +/- 2.8 ng/mg cell protein) and an HMGR activity of 111.4 +/- 7 pmol/min/m g cell protein. After binding, the LDLs were internalized and degraded by a common saturable process. The HMGR activity was higher in A549 c ells than in fibroblasts but LDL affinity and binding capacity were si milar in both cell types. However, in the presence of lipoproteins, A5 49 cells showed a two-fold higher binding capacity than fibroblasts. W hen the cells were deprived of cholesterol, the amount of LDLR sites i ncreased but the extent of stimulation was lower in A549 than in fibro blast cells (2.5-fold versus six-fold respectively). This increase was accompanied by a similar increase in the specific LDLR mRNA cellular levels (two-fold versus six-fold respectively). When cells were depriv ed of exogenous and endogenous cholesterol (biosynthesis blocked by co mpactin), the binding capacity and the LDLR mRNA levels were yet again increased in A549 cells but not in fibroblasts. Taken together these results suggest that the level of expression of the LDLR is up-regulat ed in A549 cells compared to fibroblasts.