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Estrogen receptors in human myeloma cells
T Otsuki1, O Yamada, J Kurebayashi
1Department of Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan. takemi@med.kawasaki-m.ac.jp
Abstract:
It has recently been reported that the human myeloma cell line U266 proceeds to undergo apoptosis after cultivation with the antiestrogen tamoxifen, thus raising the possibility that antiestrogens may be candidates for use in myeloma therapy. To obtain basic information on the effects of antiestrogens on myeloma cells, we investigated the mRNA expression levels of estrogen receptor (ER)-alpha, ER-beta, and coactivators and corepressors in nine human myeloma cell lines and compared them with those of seven human breast cancer cell lines including four ER-positive and three ER-negative lines. The alterations in cell growth and mRNA expression of the target genes of ER or those of cytokines in the myeloma lines by estradiol or antiestrogens (tamoxifen and toremifene) were also investigated. In addition, effects on membrane Fas expression, appearance of apoptosis, and cell cycle perturbation were analyzed. It was revealed that ER-beta and corepressors were dominantly expressed in myeloma cells, and antiestrogens induced growth inhibition through apoptosis mediated by a Fas-related pathway and G1 arrest of the cell cycle in myeloma cell lines.
Insights
Antiestrogens like tamoxifen show potential in treating myeloma. They induce cancer cell death via apoptosis and cell cycle arrest, offering a new therapeutic avenue for this blood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The human myeloma cell line U266 undergoes apoptosis when treated with tamoxifen.
- This suggests antiestrogens may be viable therapeutic agents for myeloma.
- Estrogen receptors (ERs) and their associated proteins play roles in various cancers.
Purpose of the Study:
- To investigate the effects of antiestrogens on myeloma cells.
- To determine the expression levels of estrogen receptors (ER)-alpha and ER-beta, coactivators, and corepressors in human myeloma cell lines.
- To explore the potential of antiestrogens in myeloma therapy.
Main Methods:
- Investigated mRNA expression of ER-alpha, ER-beta, coactivators, and corepressors in nine human myeloma and seven breast cancer cell lines.
- Analyzed alterations in cell growth and gene expression induced by estradiol and antiestrogens (tamoxifen, toremifene).
- Assessed effects on membrane Fas expression, apoptosis, and cell cycle progression.
Main Results:
- Estrogen receptor (ER)-beta and corepressors were predominantly expressed in myeloma cells.
- Antiestrogens (tamoxifen, toremifene) significantly inhibited myeloma cell growth.
- Growth inhibition was mediated by apoptosis, involving a Fas-related pathway and G1 cell cycle arrest.
Conclusions:
- Myeloma cells predominantly express ER-beta and corepressors.
- Antiestrogens induce myeloma cell apoptosis and G1 cell cycle arrest.
- Antiestrogens represent a promising therapeutic strategy for myeloma treatment.