| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
First of all, the endometrial specimens of 34 (25 premenopausal and 9 postmenopausal) breast cancer patients receiving tamoxifen (TAM) could be immunohistochemically examined, using estrogen receptor (ER), progesterone receptor (PR), Ki67 and epidermal growth factor receptor (EGFR) antibodies. The ER and PR expressions of the glandular cells in TAM-treated patients did not differ from those of the glandular cell in the control women regardless of menopausal status. The Ki67 index of glandular cells in TAM-induced amenorrheic women was found to be lower than that of the proliferative glandular cells in the control women (P<0.03). The Ki67 index of glandular cells in the TAM-treated postmenopausal patients was higher than that of the glandular cells in the control women (P<0.02). No activation of EGFR expression showed in glandular cells of the TAM-treated premenopausal patients, but expression of EGFR was high in glandular cells of the TAM-treated postmenopausal patients associated with
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high Ki67 index. In competition with ovarian estrogen secretion, TAM may have an antiestrogenic effect on the endometrium, but TAM probably has an estrogenic effect in abscence of ovarian estrogen secretion. This estrogenic effect of TAM may be associated with EGFR autocrine system. Second, we evaluated the proliferation and apoptosis of the endometirum throughout the menstrual cycle. Tissue specimens were collected from 30 premenopausal women. The sections were immunohistochemically examined using the antibodies of c-jun protein, c-fos protein, estrogen receptor α (ERα), progesterone receptor (PR), Ki-67, and BAX.In the proliferative phase, both glandular epithelial and stromal cells showed a high expression of c-jun protein, c-fos protein, ERα, PR and the Ki-67 index, and a low expression of BAX.In the late secretory phase, the glandular epithelial cells showed a negative expression of c-jun protein, ERα, PR, and for the Ki-67 index, and a high expression of BAX and c-fos protein, while the predecidualized stromal cells showed a high expression of c-jun protein, c-fos protein, and PR and a low expression of BAX and a negative expression for the Ki-67 index. The cyclic change of c-jun protein is thus considered to probably play an important role in the proliferation and apoptosis of glandular epithelial and stromal cells. Less
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