Differential expression of LR11 during proliferation and differentiation of cultured neuroblastoma cells

An involvement of the low density lipoprotein receptor (LDLR) gene family i n both intracellular signal pathways for neural organization and metabolic pathways for lipoprotein homeostasis is now well established. The discovery of LR11, a mosaic LDLR family member offers the opportunity to gain new in sights into receptor multifunctionality, Here, we studied the proliferation -dependent expression of LR11 mRNA and protein using two cultured cell line s, IMR32 neuroblastoma and PC12 pheochromocytoma. Within 24 h, the LR11 pro tein rose 1.9-fold in proliferating IMR32 cells, and increased further to 5 .3-fold at 72 h, This conformed with a transcript level increase of 4.7-fol d at 72 h in the proliferating cells. On the other hand, under differentiat ion conditions, a 2.9-fold increase was observed within 24 h, but at 72 h t hereafter the protein levels decreased to 60% of control. The transcript al so increased to 1.8-fold within 24 h, and then decreased to 1.1-fold at 72 h, In order to assess the transcriptional activities of the LR11 gene, we i dentified the 5'-flanking region of the murine LR11 gene. Transfection of I MR32 and PC12 cells with plasmids containing the whole or deleted fragments of 5'-flanking region showed that element(s) responsible for the above des cribed different transcriptional activities are located in the upstream seq uence between -861 and -396. Thus, the transcription of LR11 in these two c ell systems Is regulated differently during proliferation and differentiati on, suggesting that the multifunctionality of LR11, as well as other LDLR f amily members, for rapid cell growth in malignant cells and neural outgrowt h in cultured neurons, respectively, The possible involvement of LR11 in ce llular proliferation and differentiation sheds new right on its functions c ells. (C) 2000 Academic Press.