Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Int J Gynecol Cancer. 2011 Jul;21(5):800-5. doi: 10.1097/IGC.0b013e31821a2584.
The objective of the study was to determine the expression of HOXA10 in human endometrial tissue in endometrial hyperplasia and carcinomas, and regulation by sex steroids in Ishikawa cells.
Endometrial tissue was obtained from 133 subjects with normal endometria, endometrial hyperplasia, or endometrial adenocarcinoma. Among 133 specimens, 20 were normal endometria, 19 were simple hyperplasias without atypia, 20 were complex hyperplasias without atypia, 33 were atypical hyperplasias, and 41 were endometrial adenocarcinomas. The expression of HOXA10 was analyzed by immunohistochemistry. Ishikawa cell lines were incubated with 17β estradiol (10⁻⁸ mol/L) alone, medroxyprogesterone acetate (10⁻⁶ mol/L) alone, or the combination of estrogen and progesterone for 48 hours, respectively. In certain experiments, the antiprogestin antagonist, RU486 (10⁻⁵ mol/L), was also added to Ishikawa cells along with estradiol and medroxyprogesterone acetate for 48 hours. The expression of HOXA10 gene was detected by reverse transcriptase-polymerase chain reaction and Western blotting.
HOXA10 was expressed in both normal and neoplastic endometria. No significant difference in HOXA10 expression was found between normal and hyperplastic endometrial tissues. The expression of HOXA10 was decreased in endometrial adenocarcinomas compared with normal endometria. Estrogen alone, progestin alone, or progestin combined with estrogen could significantly increase the expression of HOXA10 gene (P<0.05). RU486 could inhibit the effect of up-regulation of HOXA10 expression by progestin.
The expression of HOXA10 was deregulated in endometrial carcinomas and up-regulated by sex hormones.
本研究旨在检测 HOXA10 在子宫内膜增生和癌组织中的表达,并探讨其在 Ishikawa 细胞中受性激素调控的情况。
本研究共纳入 133 例正常子宫内膜、子宫内膜增生和子宫内膜腺癌患者的子宫内膜组织标本。其中,20 例为正常子宫内膜,19 例为单纯性非典型增生,20 例为复杂性非典型增生,33 例为不典型增生,41 例为子宫内膜腺癌。采用免疫组织化学方法检测 HOXA10 的表达。Ishikawa 细胞系分别用 17β 雌二醇(10⁻⁸mol/L)、醋酸甲羟孕酮(10⁻⁶mol/L)或雌孕激素联合处理 48 小时,在某些实验中,还在 Ishikawa 细胞中加入孕激素拮抗剂 RU486(10⁻⁵mol/L),与雌二醇和醋酸甲羟孕酮共同孵育 48 小时。采用逆转录聚合酶链反应和 Western blot 检测 HOXA10 基因的表达。
HOXA10 在正常和肿瘤子宫内膜中均有表达。正常和增生子宫内膜组织中 HOXA10 的表达无显著差异。与正常子宫内膜相比,子宫内膜腺癌中 HOXA10 的表达降低。雌激素、孕激素或雌孕激素联合处理均可显著增加 HOXA10 基因的表达(P<0.05)。RU486 可抑制孕激素上调 HOXA10 表达的作用。
HOXA10 在子宫内膜癌中表达失调,并受性激素调控。