A pure antiestrogen, ICI 182,780, stimulates the growth of tamoxifen-resistant KPL-1 human breast cancer cells in vivo but not in vitro

被引:18
作者
Kurebayashi, J
Otsuki, T
Yamamoto, S
Kurosumi, M
Nakata, T
Akinaga, S
Sonoo, H
机构
[1] Kawasaki Med Sch, Dept Breast & Thyroid Surg, Okayama 7010192, Japan
[2] Kawasaki Med Sch, Dept Hyg, Okayama, Japan
[3] Saitama Canc Ctr, Dept Pathol, Ina, Saitama 362, Japan
[4] Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Shizuoka, Japan
关键词
antiestrogen; resistance; breast cancer; cell line; fibroblast growth factor-1;
D O I
10.1159/000055256
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The critical mechanisms responsible for antiestrogen resistance have not yet been elucidated. We previously established a breast cancer cell line, KPL-1, derived from a patient with recurrent disease which appeared under tamoxifen administration. In a previous study, we suggested that this cell line is estrogen receptor (ER)-positive but tamoxifen-resistant. In the present study, the effects of a pure antiestrogen, ICI 182,780, on this cell line were investigated. Although tamoxifen inhibited neither cell growth nor estradiol-stimulated transcriptional activity in vitro, ICI 182,780, significantly inhibited both of them. Tamoxifen and ICI 182,780 were then administered to female nude mice bearing KPL-1 tumors. Tamoxifen had no effect on tumor growth, but ICI 182,780 unexpectedly stimulated it (p=0.022). Estradiol tended to inhibit tumor growth (p=0.198). Immunohistochemical analysis revealed that ICI 182,780 significantly increased the Ki67-labeling index (p<0.001) but estradiol decreased it (p=0.035). To explore the possible mechanisms of these phenotypes, the mRNA levels of ER-alpha, ER-beta, transforming growth factor-beta 1, fibroblast growth factor (FGF)-1 and FGF-4 in KPL-1 cells were compared with those in other ER-positive human breast cancer cell lines by reverse-transcription polymerase chain reaction. FGF-I was overexpressed only in KPL-1 cells. This cell line is the first breast cancer cell line to be growth-stimulated by ICI 182,780 in vivo. Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells.
引用
收藏
页码:23 / 33
页数:11
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