Ishikawa Atsuko, Kudo Mitsuhiro, Nakazawa Nando, Onda Munehiko, Ishiwata Toshiyuki, Takeshita Toshiyuki, Naito Zenya
Female Reproductive and Developmental Medicine, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
Int J Oncol. 2008 Mar;32(3):565-74.
The keratinocyte factor (KGF) and its receptor (KGFR) are implicated in tissue development and repair. We studied the expression and functions of KGF and KGFR in association with estrogen and progesterone in human endometrial tissues and cells. In non-cancerous human endometrial tissues in the secretory phase, a strong immunoreactivity of KGF in glands, stromal cells, and smooth muscle cells of spiral arteries was detected; however, in proliferative-phase tissues, the immunoreactivity of KGF or KGFR was weak or absent. Most of the 32 endometrioid adenocarcinoma cases showed positive KGF and KGFR stainings (90.6 and 71.9%, respectively). We then studied, using Ishikawa well-differentiated human endometrial cancer cell line that expresses estrogen receptor (ER) and progesterone receptor (PR), the expression of KGF and KGFR in conjunction with estrogen and progesterone, and observed that the KGFR expression of Ishikawa cells was upregulated by estrogen and that this upregulation was markedly enhanced by the coadministration of progesterone. We also observed that KGF administration to cells, with KGFR upregulated expression, stimulated ERK1/2 phosphorylation and cell adhesion to fibronectin. The implications of the hormone-stimulated KGF-KGFR expressions in the regulation of cell behavior associated with human endometrial cancer are discussed.
角质形成细胞生长因子（KGF）及其受体（KGFR）与组织发育和修复有关。我们研究了KGF和KGFR在人子宫内膜组织和细胞中与雌激素和孕激素相关的表达及功能。在分泌期的非癌性人子宫内膜组织中，检测到KGF在腺体、基质细胞和螺旋动脉平滑肌细胞中有强烈的免疫反应性；然而，在增殖期组织中，KGF或KGFR的免疫反应性较弱或不存在。32例子宫内膜样腺癌病例中的大多数显示KGF和KGFR染色阳性（分别为90.6%和71.9%）。然后，我们使用表达雌激素受体（ER）和孕激素受体（PR）的Ishikawa高分化人子宫内膜癌细胞系，研究了KGF和KGFR与雌激素和孕激素联合时的表达，并观察到Ishikawa细胞的KGFR表达被雌激素上调，且这种上调在同时给予孕激素时显著增强。我们还观察到，对KGFR表达上调的细胞给予KGF可刺激ERK1/2磷酸化和细胞与纤连蛋白的黏附。本文讨论了激素刺激的KGF-KGFR表达在调节与人子宫内膜癌相关的细胞行为中的意义。
