Phytoestrogen-mediated inhibition of proliferation of the human T47D breast cancer cells depends on the ERα/ERβ ratio

Autor: P. T. Van Der Saag, D. Ratman, Albertinka J. Murk, Jan-Åke Gustafsson, J.J.M. Vervoort, A. M. Sotoca, Ivonne M.C.M. Rietjens, Anders Ström
Rok vydání: 2008
Předmět:
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Genistein
Estrogen receptor
Toxicology
Biochemistry
quercetin
chemistry.chemical_compound
Endocrinology
polycyclic compounds
Receptor
luciferase reporter
reproductive and urinary physiology
prostate
Estradiol
modulation
Molecular Medicine
hormones
hormone substitutes
and hormone antagonists
Intracellular
endocrine system
medicine.medical_specialty
Biochemie
Breast Neoplasms
Phytoestrogens
Biology
estrogen-receptor-beta
genistein
Cell Line
Tumor
Internal medicine
expression
medicine
Estrogen Receptor beta
Humans
Molecular Biology
Toxicologie
Estrogen receptor beta
Cell Proliferation
VLAG
Cell growth
Estrogen Receptor alpha
Cell Biology
Tetracycline
nuclear
recruitment
chemistry
Cell culture
Cancer research
line
Estrogen receptor alpha
Zdroj: Journal of Steroid Biochemistry and Molecular Biology, 112(4-5), 171-178
Journal of Steroid Biochemistry and Molecular Biology 112 (2008) 4-5
ISSN: 0960-0760
DOI: 10.1016/j.jsbmb.2008.10.002
Popis: This study investigates the importance of the intracellular ratio of the two estrogen receptors ERalpha and ERbeta for the ultimate potential of the phytoestrogens genistein and quercetin to stimulate or inhibit cancer cell proliferation. This is of importance because (i) ERbeta has been postulated to play a role in modulating ERalpha-mediated cell proliferation, (ii) genistein and quercetin may be agonists for both receptor types and (iii) the ratio of ERalpha to ERbeta is known to vary between tissues. Using human osteosarcoma (U2OS) ERalpha or ERbeta reporter cells it was shown that compared to estradiol (E2), genistein and quercetin have not only a relatively greater preference for ERbeta but also a higher maximal potential for activating ERbeta-mediated gene expression. Using the human T47D breast cancer cell line with tetracycline-dependent ERbeta expression (T47D-ERbeta), the effect of a varying intracellular ERalpha/ERbeta ratio on E2- or pythoestrogen-induced cell proliferation was characterised. E2-induced proliferation of cells in which ERbeta expression was inhibited was similar to that of the T47D wild type cells, whereas this E2-induced cell proliferation was no longer observed when ERbeta expression was increased. With increased expression of ERbeta the phytoestrogen-induced cell proliferation was also reduced. These results point at the importance of the cellular ERalpha/ERbeta ratio for the ultimate effect of (phyto)estrogens on cell proliferation.
Databáze: OpenAIRE
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