ESTROGEN-INDUCED KERATINOCYTE GROWTH-FACTOR MESSENGER-RNA EXPRESSION IN NORMAL AND CANCEROUS HUMAN BREAST CELLS

The local recurrence rate of breast cancer has been reported to be unu sually high at the surgical scar. Such breast cancer recurrence is bel ieved to be triggered by the release of growth factors into the healin g 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 p urpose of the present study was to determine the effect of estradiol-1 7 beta on KGF gene expression in normal human breast stromal cells, as well as in human breast cancer stromal cells, and the mechanisms by w hich estradiol-17 beta regulates breast epithelial proliferation. Our results show that KGF expression was not effected by estradiol-17 beta treatment in normal human breast stromal cells. In contrast, KGF expr ession was stimulated by estradiol-17 beta in human breast cancer stro mal cells. KGF mRNA levels have also been examined in normal human bre ast stromal cells and human breast cancer stromal cells. An interestin g correlation was found between KGF expression and estradiol-17 beta r egulation in these cell types. Normal human breast stromal cells which do not response to estradiol-17 beta have lower KGF mRNA level than t he cancer cells which KGF expression is stimulated by estradiol-17 bet a. 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 est radiol-17 beta induces KGF mRNA expression in human breast cancer stro mal cells, KGF may be involved at least in part in the stimulatory pat hway that is initiated by estradiol-17 beta in human breast cancer epi thelial cells.