Importin 13在子宫内膜异位症和子宫内膜癌中的表达及意义

背景与目的:正常情况下的子宫内膜干/祖细胞有助于子宫内膜的生理性修复,而子宫内膜干/祖细胞的异常增殖和异常分化则会导致子宫内膜疾病(如子宫内膜异位症和子宫内膜癌)。Importin 13(IPO13)是importinβ家族新成员的一个核质双向的转运受体蛋白,是角膜上皮干细胞的一个标记,在维持干细胞的性状、高增殖潜力、低分化状态,调节细胞分化以及小鼠生殖细胞减数分裂上具有重要的作用。本文探讨成体干细胞标记IPO13在子宫内膜异位症和子宫内膜癌中的表达及意义。方法:手术取正常子宫内膜组织40例(对照组),其中增生期和分泌期各20例,异位子宫内膜组织20例(异位症组)和子宫内膜癌病灶组织20例(内膜癌组)。采用免疫组化SP法检测IPO13蛋白在细胞内的定位;采用实时荧光定量PCR技术(real-time quantitativepolymerase chain reaction,RT-PCR)检测IPO13 mRNA的表达;Western blot检测IPO13蛋白的表达。结果:IPO13蛋白在内膜癌、异位症及正常对照组中腺上皮细胞和间质细胞的细胞质和细胞核中均有表达。IPO13蛋白在对照组增生期表达量(0.52±0.30)明显高于分泌期(0.25±0.04,P<0.05);IPO13蛋白在异位症组表达量(0.81±0.12)明显高于对照组增生期及分泌期(P<0.05);IPO13蛋白在内膜癌组表达量(1.21±0.11)明显高于异位症组(P<0.05)。IPO13 mRNA在对照组增生期表达量是分泌期的3倍(P<0.05);IPO13 mRNA在异位症组中表达量是对照组分泌期的6倍(P<0.05),增生期的2.5倍(P<0.05);IPO13 mRNA在内膜癌组表达量是异位症组的2倍(P<0.05)。结论:IPO13在子宫内膜癌中及异位症组中表达明显高于对照组,推测其高表达与子宫内膜癌及子宫内膜异位症发病密切相关。

The expression and significance of importin 13 in endometriosis and endometrial carcinoma

Background and purpose:Human uterine stem/progenitor cells activity contributes to the physiological endometrial repair,but abnormal proliferation and abnormal differentiation of uterine stem/progenitor cells will lead to endometrial disease(such as endometriosis and endometrial carcinoma).Importin 13(IPO13) is the new family member of importin β,a two-way transfer of nuclear receptor proteins and a marker of corneal epithelial stem cells.In the maintenance of stem cells,high proliferative potential and poorly differentiated state play important roles in regulating normal and abnormal of cell differentiation and mouse germ cells meiosis.The study investigated the expression of IPO13 gene,an adult stem cell marker,in endometriosis and endometrial carcinoma tissues for the purpose of finding the relationship between this gene and endometriosis and endometrial carcinoma.Methods:The expression of IPO13 in normal endometrial tissues,endometriosis tissues and endometrial carcinoma tissues was detected by the immunohistochemistry,real-time PCR and Western blot respectively.Results:In endometrial carcinoma,endometriosis and control groups,the expression of IPO13 protein was found in cytoplasm and nucleus of epithelial cells and stromal cells.The expression level of IPO13 protein in normal proliferative phase endometrium was 0.52±0.30,significantly higher than that in normal secretory phase(0.25±0.04,P<0.05);IPO13 protein in the ectopic endometrium was 0.81±0.12,significantly higher than that in proliferative phase and secretory phase endometria(P<0.05);IPO13 protein in the endometrial carcinoma was 1.21±0.11,significantly higher than that in the ectopic endometrium(P<0.05).The expression level of IPO13 mRNA in normal proliferative phase endometrium was 3 times higher than that in normal secretory phase(P<0.05);IPO13 mRNA in the ectopic endometrium was 2.5 times higher than that in normal proliferative phase endometrium and 6 times higher than that in normal secretory phase endometrium(P<0.05);IPO13 mRNA in the endometrial carcinoma were 2 times higher than that in the ectopic endometrium(P<0.05).Conclusion:The expression of IPO13 in endometrial carcinoma and endometriosis is increased,which suggests IPO13 is closely related with endometrial cancer and endometriosis.