Yang Xiaojing, Ren Hanru, Yao Li, Chen Xueyu, He Aina
Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600, Yishan Road, Shanghai, 200233, China,
Tumour Biol. 2015 May;36(5):3717-26. doi: 10.1007/s13277-014-3011-9. Epub 2015 Jan 5.
Eps15 homology domain-containing 2 (EHD2) is a tumor suppressor gene, overexpressed in several solid tumors, including ovarian cancer and esophageal squamous cell carcinoma. The current study examined the expression and the role of EHD2 in human breast cancer. EHD2 expression was determined by Western blot and immunohistochemistry (IHC) in 80 breast cancer and paired noncancerous breast tissues. Correlations between clinicopathologic variables, overall survival, and EHD2 expression were analyzed. We investigated the role of EHD2 in breast cancer migration and invasion by wound healing assay and trans-well invasion assays. A notably lower level of EHD2 expression was found in breast cancer tissues. EHD2 expression was associated with histological grade, lymph node metastasis, and tumor size. Expression of EHD2 was found to be an independent prognostic factor in breast cancer patients. Furthermore, overexpression of EHD2 suppressed, while elimination of EHD2 promoted, the migration and invasion of breast cancer cells. Molecular data showed that EHD2 inhibited breast cancer migration and invasion probably by dampening the expression of Ras-related C3 botulinum toxin substrate 1 (Rac1). Downregulation of EHD2 was associated with migration and invasion by abrogating the expression of Rac1 in breast cancer patients. EHD2 may serve as a prognostic marker in breast cancer.
含Eps15同源结构域2（EHD2）是一种肿瘤抑制基因，在包括卵巢癌和食管鳞状细胞癌在内的多种实体瘤中过表达。本研究检测了EHD2在人乳腺癌中的表达及作用。采用蛋白质免疫印迹法和免疫组织化学（IHC）法检测80例乳腺癌组织及配对的癌旁乳腺组织中EHD2的表达。分析临床病理变量、总生存期与EHD2表达之间的相关性。通过伤口愈合试验和Transwell侵袭试验研究EHD2在乳腺癌迁移和侵袭中的作用。结果发现乳腺癌组织中EHD2表达水平显著降低。EHD2表达与组织学分级、淋巴结转移和肿瘤大小相关。EHD2表达是乳腺癌患者的独立预后因素。此外，EHD2过表达抑制乳腺癌细胞的迁移和侵袭，而EHD2缺失则促进其迁移和侵袭。分子数据显示，EHD2可能通过抑制Ras相关C3肉毒杆菌毒素底物1（Rac1）的表达来抑制乳腺癌的迁移和侵袭。在乳腺癌患者中，EHD2下调与通过消除Rac-1表达而导致的迁移和侵袭有关。EHD2可能作为乳腺癌的预后标志物。
