Paradoxial changes in the expression of estrogen receptor alpha in breast cancer multicellular spheroids

被引:5
作者
Munoz, Laura [2 ]
Espinosa, Magali [1 ]
Quintanar-Jurado, Valeria [1 ]
Hidalgo, Alfredo [1 ]
Melendez-Zajgla, Jorge [1 ]
Maldonado, Vilma [2 ]
机构
[1] Natl Inst Genom Med, Mexico City 01900, DF, Mexico
[2] Natl Inst Cancerol, Mol Biol Lab, Subdirect Basic Res, Mexico City 14080, DF, Mexico
关键词
Multicellular spheroids; Three-dimensional culture; Estrogen receptor; Breast cancer; DOWN-REGULATION; CELLS; PROLIFERATION; RESISTANCE;
D O I
10.1016/j.tice.2010.07.006
中图分类号
R602 [外科病理学、解剖学]; R32 [人体形态学];
学科分类号
100101 ;
摘要
Multicellular spheroids are excellent models for the analysis of cancer behavior. Just like small avascular tumors, they present a marked zonal heterogeneity which influences gene expression and thus, growth and response to chemotherapy. In the present paper, we sought to analyze the effects of three-dimensional culture in the expression and distribution of estrogen receptor alpha. Using MCF-7 breast cancer cells, we found that multicellular spheroids in estrogen-containing medium presented a paradoxical regulation of estrogen receptor alpha, with a decrease in protein expression and a marked increase in mRNA steady-state levels. Immunohistochemistry showed that only sparse cells in the periphery of the spheroid expressed estrogen receptor, in sharp contrast with progresterone receptor, which was more extensively expressed and HIF-alpha, which was expressed in the central core of the spheroid. This could mean that both hypoxia and ERA activation by estrogen participate in the expression heterogeneity of this hormone receptor in breast cancer These results are important to considerate in the analysis and interpretation of immunohistochemistry of ERA and downstream targets in samples of solid tumors. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:334 / 337
页数:4
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