Investigation of in situ estrogen metabolism and estrogen responsive gene in endometrial cancer : New aspects of hormone therapy

雌激素的原位代谢和合成在人类子宫内膜癌的发生发展中起着非常重要的作用。然而，在子宫内膜癌中，雌激素组织浓度和肿瘤内酶状态之间的相关性尚未被研究。因此，在本研究中，我们检测了绝经后子宫内膜癌患者癌组织和血浆中雌二醇(E_1)、雌二醇(E_2)和睾酮的浓度以及癌组织中的酶活性。子宫内膜癌组织中的E_1、E_2和睾酮水平均显著高于血清。子宫内膜癌组织中有17种不同类型的酶表达，包括17种β-羟基类固醇脱氢酶2型(17种β-HSD2型)、17种β-HSD5型、类固醇硫酸酯酶、雌激素磺基转移酶和芳香化酶。17例β-HSD2型基因表达水平与肿瘤内雌二醇浓度呈显著负相关。肿瘤组织睾酮和芳香酶基因表达水平呈显著负相关。这些结果表明，几种肿瘤内酶的表达，特别是17β-HSD2型和芳香化酶，与子宫内膜癌中的雌激素水平有关。此外，我们的结果提示，17个β-HSD2型的原位表达可以预测子宫内膜癌患者对孕激素治疗的可能反应。总之，子宫内膜癌的雌激素生物合成途径与乳腺癌有很大的不同。利用基因芯片，我研究了雌激素在乳腺和子宫内膜癌细胞系中的表达。我还认为，乳腺癌和子宫内膜癌在雌激素反应基因表达方面存在很大差异，这些基因表达与各种行为有关。

In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinomas. 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. Various types of intratumorall enzymes expression which included 17 β-hydroxysteroid dehydrogenase type 2 (17 β-HSD type 2), 17 β-HSD type 5, steroid sulfatase, estrogen sulfotransferase and aromatase, were observed in endometrial carcinoma. There was a statistically significant inverse correlation between intratumoral estradiol concentration and the level of 17 β-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 17 β-HSD type 2 and aromatase, contribute to intratumoral estrogen levels in human endometrial carcinoma. Moreover, our results suggested that in situ abundance of 17 β-HSD type 2 can predict the possible response of patients with endometrial carcinoma to progestogen treatment. In summary, Estrogen biosynthesis pathway in endometrial cancers is quite different from that in breast cancers. Using cDNA microarrays, I investigated estrogen responsive gene expression in breast and endometrial cancer cell lines. 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.