Estrogen receptor α mediated induction of the transforming growth factor α gene by estradiol and 4-hydroxytamoxifen in MDA-MB-231 breast cancer cells

Autor: Anait S. Levenson, Jun Horiguchi, Jennifer MacGregor Schafer, V. Craig Jordan, Zehan Chen, Hong Liu
Rok vydání: 2001
Předmět:
medicine.medical_specialty
TGF alpha
DNA
Complementary
Time Factors
Transcription
Genetic
genetic structures
Endocrinology
Diabetes and Metabolism
Blotting
Western
Clinical Biochemistry
Estrogen receptor
Enzyme-Linked Immunosorbent Assay
Cycloheximide
Biology
Transfection
Biochemistry
chemistry.chemical_compound
Endocrinology
Internal medicine
Tumor Cells
Cultured
medicine
Estrogen Receptor beta
Humans
RNA
Messenger
Luciferases
Molecular Biology
Estrogen receptor beta
Protein Synthesis Inhibitors
Dose-Response Relationship
Drug
Estradiol
Estrogen Antagonists
Estrogen Receptor alpha
Cell Biology
Transforming Growth Factor alpha
Blotting
Northern
Molecular biology
Tamoxifen
Receptors
Estrogen
chemistry
Cell culture
Dactinomycin
Molecular Medicine
Estrogen receptor alpha
Signal Transduction
Transforming growth factor
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 78:41-50
ISSN: 0960-0760
DOI: 10.1016/s0960-0760(01)00072-3
Popis: The selective estrogen receptor modulator, 4-hydroxytamoxifen (4-OHT) is a full agonist at the transforming growth factor (TGF) alpha gene in ER negative breast cancer cells stably transfected with ER alpha cDNA (Levenson et al., Br. J. Cancer 77 (1998) 1812-1819). E(2) and 4-OHT increase TGF alpha mRNA and protein in a concentration dependent manner. The responses to E(2) and 4-OHT are blocked by the pure antiestrogen ICI 182,780, which does not induce TGF alpha. Transfected MDA-MB-231 cells contain functional ER alpha but no ER beta function was detected. Neo transfected cells that did not express ER alpha or cells stably transfected with the DNA binding domain mutant C202R/E203V which prevents gene activation did not induce TGF alpha mRNA after either E(2) or 4-OHT treatment. An examination of the time course for either 10 nM E(2) or 1 microM 4-OHT for MDA-MB-231 cells stably transfected with cDNA for ER alpha showed increases in TGF alpha mRNA within 2 or 3 h respectively. Cells pretreated with cycloheximide (1 microg/ml) showed induced TGF alpha mRNA in response to E(2) or 4-OHT but TGF alpha mRNA induction was blocked by actinomycin D (1 microg/ml). We conclude that both E(2) and 4-OHT induce TGF alpha by direct interaction of ER alpha with DNA and that ER beta is not involved in the estrogen-like response to 4-OHT in the MDA-MB-231 cells.
Databáze: OpenAIRE
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