Estrogen regulation of a transforming growth factor-beta inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts.
Endocrinology
; 139(3): 1346-53, 1998 Mar.
Article
em En
| MEDLINE
| ID: mdl-9492071
ABSTRACT
This laboratory reported the identification and characterization of a unique three zinc finger, transcription factor-like, transforming growth factor-beta inducible early gene (TIEG) (see Ref. 35). TIEG expression has been shown to be tissue- and cell type specific, enhanced by specific growth factors, and to decrease with advancing stages of breast cancer. Recent studies involving TIEG overexpression in pancreatic carcinoma cells indicate that TIEG expression inhibits DNA synthesis, similar to a tumor suppressor-like gene, and plays a role in apoptosis (see Ref. 37). This paper describes the rapid, but transient, induction of TIEG steady-state messenger RNA (mRNA) levels by 17beta-estradiol (E2) in estrogen receptor (ER)-positive, human fetal osteoblastic (hFOB/ER) cells. This rapid induction is shown to be ER- and steroid dose-dependent but protein synthesis independent. An antagonism between E2 and PTH, which occurs in skeletal metabolism, is shown to concur rapidly with TIEG mRNA expression. Scanning confocal microscopy (using polarized, laser-based immunofluorescence) shows that TIEG protein is localized in the nucleus of hFOB/ER cells, with the levels rapidly increasing after E2 treatment. The rapid E2-induced increase in TIEG expression is followed by an E2-induced inhibition of DNA synthesis in the hFOB/ER cells. Antiestrogens block not only the induction of TIEG mRNA levels but also the inhibition of cell proliferation. Lastly, hFOB cells, stably transfected with a TIEG expression vector, display markedly reduced DNA synthesis/cell proliferation, compared with nontransfected cells. These results support the finding that TIEG is an early responding regulatory gene for E2 in human osteoblast cells that inhibits DNA synthesis. It is speculated that TIEG may play a role in the signaling pathway for E2 in inhibiting cell proliferation.
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Base de dados:
MEDLINE
Assunto principal:
Osteoblastos
/
Fatores de Transcrição
/
DNA
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Regulação da Expressão Gênica
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Fator de Crescimento Transformador beta
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Dedos de Zinco
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Proteínas de Ligação a DNA
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Estradiol
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article