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 the metabolism of human low density lipoprotein (LDL) and 3-hydroxy-3-methyl-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 sites (KD 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/mg cell protein. After binding, the LDLs were internalized and degraded by a common saturable process. The HMGR activity was higher in A549 cells than in fibroblasts but LDL affinity and binding capacity were similar in both cell types. However, in the presence of lipoproteins, A549 cells showed a two-fold higher binding capacity than fibroblasts. When the cells were deprived of cholesterol, the amount of LDLR sites increased but the extent of stimulation was lower in A549 than in fibroblast 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 deprived of exogenous and endogenous cholesterol (biosynthesis blocked by compactin), 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-regulated in A549 cells compared to fibroblasts.
Gueddari
N
N
Laboratoire de Ciblage en Thérapeutique, Faculté des Sciences Pharmaceutiques, Toulouse, France.
Favre
G
G
Hachem
H
H
Marek
E
E
Le Gaillard
F
F
Soula
G
G
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002784:Cholesterol / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D008077:Lipoproteins, LDL / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism* / Q000502:physiology; D015183:Restriction Mapping; D012260:Ribonucleases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D012260:Ribonucleases