Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, PR China.
Oncol Rep. 2013 Aug;30(2):723-30. doi: 10.3892/or.2013.2496. Epub 2013 May 27.
The molecular mechanism involved in the metastasis of endometrial cancer (EC) remains unclear. The lysosomal cysteine protease Cathepsin B has been implicated in the progression of various human tumors. In the present study, we assessed the expression of Cathepsin B and its functions in EC. Immunohistochemistry was used to examine Cathepsin B expression in 76 paraffin-embedded endometrial tumor tissues. Lentiviral packing short hairpin RNA (shRNA) was transfected into HEC-1A cells to build a stable Cathepsin B knockdown cell line. The cellular levels of Cathepsin B mRNA and protein were detected by real-time PCR and western immunoblotting. The functions of Cathepsin B in EC cells were measured by MTT, migration and invasion assays. In additon, tumorigenicity assays were established in nude mice to study tumor growth in vivo. The results of our study showed that Cathepsin B was overexpressed in EC tissues compared with normal endometrium and endometrial atypical hyperplasia. Depletion of Cathepsin B in vitro inhibited cell proliferation, migration and invasion. Tumor formation assays confirmed that suppression of Cathepsin B inhibited the proliferation potential of HEC-1A cells in vivo, demonstrated by lower proliferation rates. These results suggest that Cathepsin B may act as an oncogene in EC, with the potential to provide a new therapeutic target for treating endometrial malignancy.
子宫内膜癌（EC）转移涉及的分子机制尚不清楚。溶酶体半胱氨酸蛋白酶 Cathepsin B 已被牵连到各种人类肿瘤的进展中。在本研究中，我们评估了 Cathepsin B 在 EC 中的表达及其功能。免疫组织化学用于检测 76 例石蜡包埋的子宫内膜肿瘤组织中的 Cathepsin B 表达。慢病毒包装短发夹 RNA（shRNA）转染到 HEC-1A 细胞中，构建稳定的 Cathepsin B 敲低细胞系。实时 PCR 和 Western 免疫印迹检测 Cathepsin B mRNA 和蛋白的细胞水平。MTT、迁移和侵袭测定法测量 Cathepsin B 在 EC 细胞中的功能。此外，建立裸鼠肿瘤生成实验以研究体内肿瘤生长。我们的研究结果表明，Cathepsin B 在 EC 组织中过度表达，与正常子宫内膜和子宫内膜非典型增生相比。体外 Cathepsin B 的耗竭抑制细胞增殖、迁移和侵袭。肿瘤形成实验证实，Cathepsin B 的抑制抑制了 HEC-1A 细胞在体内的增殖潜力，增殖速度较低。这些结果表明，Cathepsin B 可能在 EC 中作为癌基因发挥作用，为治疗子宫内膜恶性肿瘤提供了新的治疗靶点。
