Hu F, Yuan W, Wang X, Sheng Z, Yuan Y, Qin C, He C, Xu T
Department of Urology, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
Clin Transl Oncol. 2015 Aug;17(8):632-9. doi: 10.1007/s12094-015-1288-9. Epub 2015 May 20.
A novel tumor suppressor gene CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) is reduced or undetectable in many kinds of cancers and relates tumor malignant features. We detected its role in prostate cancer for possibility of target therapy as accumulating evidence has shown that CMTM3 is a promising tumor suppressor gene (TSG) for gene therapy.
The expression of CMTM3 detected in prostate tissue microarray, specimens and cell lines were evaluated by immunohistochemistry and semi-quantitative PCR and Western blot, respectively. After being transfected with CMTM3 adenovirus or vector (mock), the proliferation and migration and invasion of LNCaP cells were detected by transwell assay and matrigel assay, respectively. Furthermore, the effects of CMTM3 on tumor growth were performed in nude mice xenograft in vivo.
We found CMTM3 was reduced in PCa tissues and cells compared with BPH tissues, and its expression in PCa tissues was related to the Gleason score. Moreover, after being transfected with adenovirus, ectopic expression of CMTM3 in LNCaP cells led to significant inhibition of cell proliferation and migration and invasion compared with the control (P < 0.05), which may be attributed to decreased Erk1/2 activity as p-Erk1/2 was remarkably reduced when CMTM3 was overexpressed. Finally, restoration of CMTM3 significantly suppressed xenograft tumor growth in vivo (P < 0.01).
一种新型肿瘤抑制基因——含CKLF样MARVEL跨膜结构域成员3(CMTM3)在多种癌症中表达降低或无法检测到,且与肿瘤恶性特征相关。我们检测了其在前列腺癌中的作用,以探讨其作为靶向治疗的可能性,因为越来越多的证据表明CMTM3是一种有前景的用于基因治疗的肿瘤抑制基因(TSG)。
分别通过免疫组织化学、半定量PCR和蛋白质免疫印迹法评估前列腺组织芯片、标本及细胞系中CMTM3的表达。用CMTM3腺病毒或载体(对照)转染LNCaP细胞后,分别通过Transwell实验和基质胶实验检测细胞的增殖、迁移和侵袭能力。此外还在裸鼠体内异种移植模型中研究了CMTM3对肿瘤生长的影响。
我们发现与良性前列腺增生(BPH)组织相比,CMTM3在前列腺癌(PCa)组织及细胞中表达降低,且其在PCa组织中的表达与Gleason评分相关。此外,腺病毒转染后与对照组相比,CMTM3在LNCaP细胞中的异位表达显著抑制了细胞增殖、迁移及侵袭(P<0.05),这可能归因于Erk1/2活性降低,因为当CMTM3过表达时p-Erk1/2显著降低。最后,恢复CMTM3表达可显著抑制体内异种移植肿瘤的生长(P<0.01)。