Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St, 60-781 Poznań, Poland.
Mol Biol Rep. 2011 Jun;38(5):3355-60. doi: 10.1007/s11033-010-0441-3. Epub 2010 Nov 18.
It has recently been reported that endometrial cancer cells are able to convert estron (E1) to 17β estradiol (E2). We observed the presence of 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) transcript and protein in receptor positive ER(+) and negative ER(-) Ishikawa endometrial adenocarcinoma (ISH) cells. ER(+) ISH, but not ER(-)02 ISH, cells were significantly susceptible to apicidin induced death, and we further used ER(-)ISH cells to study the effect of apicidin on cellular levels of HSD17B1 transcript and protein. We showed that apicidin significantly lowered HSD17B1 transcript and protein levels in ISH cells. There was no significant effect on HSD17B1 transcript stability. However, chromatin immunoprecipitation analysis revealed that apicidin significantly decreased occupation of the first exon of the HSD17B1 gene by Polymerase II. Since intratumoral E1 to E2 conversion is a significant contributor to the progression of estrogen dependent cancers, and HDAC inhibitors are being tested in anticancer clinical trials, our observations may have clinical value.
最近有报道称，子宫内膜癌细胞能够将雌酮（E1）转化为 17β 雌二醇（E2）。我们观察到在受体阳性 ER（+）和阴性 ER（-）的 Ishikawa 子宫内膜腺癌（ISH）细胞中存在 17β-羟类固醇脱氢酶 1 型（HSD17B1）转录本和蛋白。ER（+）ISH 细胞，但不是 ER（-）02 ISH 细胞，对阿比西丁诱导的死亡非常敏感，我们进一步使用 ER（-）ISH 细胞来研究阿比西丁对细胞内 HSD17B1 转录本和蛋白水平的影响。结果表明，阿比西丁显著降低了 ISH 细胞中 HSD17B1 的转录本和蛋白水平。HSD17B1 转录本稳定性没有显著影响。然而，染色质免疫沉淀分析显示，阿比西丁显著降低了聚合酶 II 对 HSD17B1 基因第一外显子的占据。由于肿瘤内 E1 向 E2 的转化是雌激素依赖性癌症进展的重要因素，并且组蛋白去乙酰化酶抑制剂正在进行癌症临床试验，我们的观察结果可能具有临床价值。
