| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
We have previously shown that the sub-cellular localization of β-catenin changes according to cell proliferation of the human endometrium, suggesting a role of intercellular transduction in cell growth control in human endometrium not only in the physiological condition but also in carcinogenic endometrium. To further study the possible role of heart shock proteins (HSPs) in growth control, we immunohistochemically analyzed 92 endometrial samples, 30 of normal endometrium, 20 of endometrial hyperplasia, and 42 of endometrial cancer, for the expression of HSP27, HSP70, HSP90 and estrogen receptor (ER). In this study, HSP27 and HSP90 were detected in endometrial epithelium strongly in the proliferative phase and weakly in the secreting phase during the menstrual cycle according to the serum estradiol level. However, they, especially HSP27, were overexpressed in endometrial hyperplasia. In endometrial cancer, the expression of HSP27 was heterogenic among the glands and lower than that in
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the proliferative phase and endometrial hyperplasia. The results suggest that HSP27 and HSP90 contribute to the cell proliferation in endometrial epithelium and the phynomenon of overexpression of HSP27 in endometrial hyperplasia occurs as a result of the activated condition of ER, *gh in cancer it decreases according to the loss offunction of ER.
In another study, we focused on retinoic acid receptors (RARs and RXRs), which are ligand-dependent transcription factors that belong to the large family of steroid hormones and are expected to affect to the cell growth and differentiation in the endometrium. We analyzed the expression and subcellular localization of the RA receptors in 57 samples of human endometrium by immunohistochemistry and western blotting. In the nuclei of the endometrial epithelium, the RA receptors were expressed strongly in the proliferative phase; however, they, especially RARs, drastically decreased in the secretory phase in association with serum estradiol and the expression of estrogen receptor. The expression of RXRs was localized in the nuclei throughout the menstrual cycle. Confocal laser scanning microscopical observation clearly showed the difference of the localization between RARs and RXRs in the secretory phase, and the findings of immunoelectronmicriscopy showed pooled receptor protein around the rough endoplasmic reticulum, suggesting dysfunction of the transport of the receptors to the nuclei. These findings suggest that RARs and RXRs work mainly in the proliferative phase but that RXRs play a different role in endometrium during the secretory phase. Less
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