RRC ID 39438
Author Sasaki-Iwaoka H, Maruyama K, Endoh H, Komori T, Kato S, Kawashima H.
Title A trans-acting enhancer modulates estrogen-mediated transcription of reporter genes in osteoblasts.
Journal J. Bone Miner. Res.
Abstract The presence of bone-specific estrogen agonists and discovery of the osteoblast-specific transcription factor (TF), Cbfa1, together with the discovery of synergism between a TF Pit-1 and estrogen receptor alpha (ERalpha) on rat prolactin gene, led to investigation of Cbfa1 in the modulation of osteoblast-specific actions of estrogen. Reverse transcribed-polymerase chain reaction demonstrated expression of Cbfa1 in the osteoblastic cell lines, MG63, ROS17/2.8, and MC3T3E1, but not in nonosteoblastic cell lines, MCF7, C3H10T1/2, and HeLa. An ER expression vector and a series of luciferase (Luc) reporter plasmids harboring the Cbfa1 binding site OSE2 (the osteoblast-specific cis element in the osteocalcin promoter) and palindromic estrogen response elements (EREs) were cotransfected into both osteoblastic and nonosteoblastic cells. OSE2 worked as a cis- acting element in osteoblastic cells but not nonosteoblastic cells, whereas EREs were cis- acting in all cell lines. Synergistic transactivation was observed in osteoblastic cells only when both ERE and OSE2 were placed in juxtaposition to the promoter. Forced expression of Cbfa1 in C3H10T1/2 cells also induced synergism. Tamoxifen, a partial agonist/antagonist of estrogen, acted as an osteoblast-specific agonist in cells transfected with a promoter containing ERE and acted synergistically with a promoter containing the ERE-OSE2 enhancer combination. These results support the idea that bone-specific TFs modulate the actions of estrogen in a tissue-specific manner.
Volume 14(2)
Pages 248-55
Published 1999-2
DOI 10.1359/jbmr.1999.14.2.248
PMID 9933479
MeSH Animals Base Sequence Cell Line Core Binding Factor Alpha 1 Subunit DNA Primers / genetics Enhancer Elements, Genetic* Estrogen Antagonists / pharmacology Estrogens / metabolism* Genes, Reporter HeLa Cells Humans Luciferases / genetics Mice Neoplasm Proteins* Osteoblasts / drug effects Osteoblasts / metabolism* Rats Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Reverse Transcriptase Polymerase Chain Reaction Tamoxifen / pharmacology Transcription Factors / metabolism Transcriptional Activation / drug effects Transfection
IF 6.314
Times Cited 23
Human and Animal Cells