Estrogen-induced keratinocyte growth factor mRNA expression in normal and cancerous human breast cells.

Estrogen-induced keratinocyte growth factor mRNA expression in normal and cancerous human breast cells.
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DOI:
10.3892/or.5.3.577
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发表时间:
1998-05
期刊:
影响因子:
4.2
通讯作者:
Y. Zhang;Y. Sugimoto;S. Kulp;W. Farrar;R. Brueggemeier;Y. C. Lin
Y. Zhang;Y. Sugimoto;S. Kulp;W. Farrar;R. Brueggemeier;Y. C. Lin
中科院分区:
医学3区
文献类型:
--
作者:
Y. Zhang;Y. Sugimoto;S. Kulp;W. Farrar;R. Brueggemeier;Y. C. Lin

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据报道,乳腺癌的局部复发率在手术疤痕处异常高。这种乳腺癌复发被认为是由生长因子释放到愈合的伤口中引发的。来自动物模型的观察也表明,在小鼠皮肤中产生全层伤口显著诱导KGF表达。由于KGF是一种上皮细胞特异性的有丝分裂原在大鼠乳腺上皮,这是合理的推测,KGF也可能参与调节人类乳腺癌细胞的生长。本研究的目的是确定雌二醇-17对正常人乳腺基质细胞以及人乳腺癌基质细胞中KGF基因表达的影响,以及雌二醇-17调节乳腺上皮增殖的机制。我们的研究结果表明,KGF的表达没有受到雌二醇-17治疗在正常人乳腺基质细胞。与此相反,KGF的表达刺激雌二醇-17在人乳腺癌基质细胞。还在正常人乳腺基质细胞和人乳腺癌基质细胞中检测了KGF mRNA水平。在这些细胞类型中,发现KGF表达和雌二醇-17调节之间存在有趣的相关性。正常人乳腺基质细胞对雌二醇无反应,其KGF mRNA水平低于雌二醇刺激表达KGF的癌细胞。我们的数据还表明,重组人KGF显着刺激正常人乳腺癌和人乳腺癌上皮细胞增殖的剂量依赖性方式。由于我们已经表明,雌二醇-17诱导KGF mRNA在人乳腺癌基质细胞的表达,KGF可能参与至少部分在刺激途径,是由雌二醇-17在人乳腺癌上皮细胞启动。
The local recurrence rate of breast cancer has been reported to be unusually high at the surgical scar. Such breast cancer recurrence is believed to be triggered by the release of growth factors into the healing wound. Observations from an animal model have also demonstrated that KGF expression is dramatically induced by creation of full thickness wounds in mouse skin. Since KGF is an epithelial cell-specific mitogen in rat mammary epithelium, it is reasonable to speculate that KGF may be also involved in regulating human breast cancer cell growth. The purpose of the present study was to determine the effect of estradiol-17 on KGF gene expression in normal human breast stromal cells, as well as in human breast cancer stromal cells, and the mechanisms by which estradiol-17 regulates breast epithelial proliferation. Our results show that KGF expression was not effected by estradiol-17 treatment in normal human breast stromal cells. In contrast, KGF expression was stimulated by estradiol-17 in human breast cancer stromal cells. KGF mRNA levels have also been examined in normal human breast stromal cells and human breast cancer stromal cells. An interesting correlation was found between KGF expression and estradiol-17 regulation in these cell types. Normal human breast stromal cells which do not response to estradiol-17 have lower KGF mRNA level than the cancer cells which KGF expression is stimulated by estradiol-17. Our data also demonstrate that recombinant human KGF significantly stimulate normal human breast and human breast cancer epithelial cell proliferation in a dose-dependent manner. Since we have shown that estradiol-17 induces KGF mRNA expression in human breast cancer stromal cells, KGF may be involved at least in part in the stimulatory pathway that is initiated by estradiol-17 in human breast cancer epithelial cells.