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.

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