子宮内膜・乳腺局所での性ステロイド合成代謝経路の解明 : 組織・臓器特異性を中心に(<特集>第57回学術講演会シンポジウム: ホルモン補充療法-その基礎と臨床-)
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Women's Health Initiative Study demonstrated the possible increased risk of breast cancer associated with hormone replacement therapy (CEE plus MPA). But this risk is not increased in cases of endometrial cancer. They also demonstrated that breast cancer risk was not increased with estrogen only replacement therapy. Both Endometrial and Breast cancers are so called, "Estrogen Dependent Tumor". What is the difference between these two types of estrogen dependent cancer? I analyzed the potential differences of these two cancers. In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human breast and endometrial carcinomas. It is well known that the concentrations of estrogen in breast cancer tissue were significantly higher than those in serum. The correlation between tissue concentrations of estrogens and status of intratumoral enzymes has, however, not been examined in endometrial carcinoma. Therefore, in this study, we examined the concentrations of estrone (E1), estradiol (E2), and testosterone in carcinoma tissue and plasma as well as intratumoral enzymes activities in carcinoma tissues of postmenopausal patients with endometrial carcinoma. The concentrations of E1, E2 and testosterone in endometrial cancer tissue were significantly higher than those in serum. mRNA expression for aromatase and 17β-HSD type 2 was detected in 74% and 52% of the cases examined respectively. There was a statistically significant inverse correlation between intratu-moral estradiol concentration and the level of 17β-HSD type 2 mRNA. A statistically significant inverse correlation was detected between tumor tissue testosterone and aromatase mRNA expression level. These results suggest that several intratumoral enzymes expression, especially 17β-HSD type 2 and aromatase, contribute to intratumoral estrogen levels in human endometrial carcinoma. Estrogens are interchanged by two enzymes, 17β-HSD type 1 converts estrone to estradiol, and type 2 does the reverse actions. In breast cancer, only type 1 enzyme is expressed, whereas type 2 was not detected in any of the breast cancer cell. On contrast to breast cancer, type 1 HSD was not detected at all, but type 2 expression was detected in endometrial tissue. This is a major difference in terms of estrogen biosynthesis in breast and endometrial carcinoma tissues. Using cDNA microarrays, I also suggest that there are large amount of differences between breast and endometrial cancers, regarding estrogen responsive gene expression, which are associated with various actions.
- 社団法人日本産科婦人科学会の論文
- 2005-12-01
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