Role of tyrosine kinase signaling in estrogen-induced LDL receptor gene expression in HepG2 cells.
The expression of the low-density lipoprotein receptor (LDL-r) gene is stimulated by estrogen in vivo, although its promoter does not contain a classical estrogen-responsive element, suggesting an alternative mechanism of estrogen-regulated expression of this gene. The aim of this work was to assess whether estrogen-stimulated transcription of the LDL-r gene depends on tyrosine kinase (TK) and protein kinase C (PKC) activation, both signaling pathways being activated by estrogen in vivo and in hepatoma cells. Therefore, in HepG2 cells cotransfected with estrogen receptor-alpha, estrogen-stimulated transcription of LDL-r-promoter reporter plasmid was analyzed in the absence and presence of TK and PKC inhibitors. The expression of LDL-r was also compared with the transcription of the complement gene, which contains a classical estrogen-responsive element sequence. Our results demonstrate that the induction of LDL-r expression by estrogen requires longer stimulation than that necessary for complement induction. Moreover, basal transcription of the LDL-r gene depends on PKC activity, while estrogen-stimulated activation of the LDL-r-promoter requires TK activity, pointing to a role of these non-classical estrogen-stimulated pathways in the transcriptional regulation of the LDL-r.
Distefano
Enza
E
Dipartimento di Biologia, Università Roma Tre V. le G. Marconi, Rome, Italy.
Marino
Maria
M
Gillette
Jennifer A
JA
Hanstein
Bettina
B
Pallottini
Valentina
V
Brüning
Jens
J
Krone
Wilhelm
W
Trentalance
Anna
A
D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D011973:Receptors, LDL / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D047628:Estrogen Receptor alpha; D004967:Estrogens; D011960:Receptors, Estrogen; D011973:Receptors, LDL; D004958:Estradiol; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C