Decreased REG1α expression suppresses growth, invasion and angiogenesis of bladder cancer

J Geng; J Fan; Q Wang; X-P Zhang; L Kang; Q-Y Li; Y-F Xu; B Peng; J-H Zheng; X-D Yao

doi:10.1016/j.ejso.2017.01.013

Decreased REG1α expression suppresses growth, invasion and angiogenesis of bladder cancer

Eur J Surg Oncol. 2017 Apr;43(4):837-846. doi: 10.1016/j.ejso.2017.01.013. Epub 2017 Feb 2.

Authors

J Geng¹, J Fan², Q Wang³, X-P Zhang³, L Kang³, Q-Y Li⁴, Y-F Xu³, B Peng³, J-H Zheng³, X-D Yao⁵

Affiliations

¹ Department of Urology, Tenth People's Hospital, Tongji University, Shanghai, 200072, China. Electronic address: gengjiangsn@sina.com.
² Department of Pathology, Huashan Hospital, Fudan University, Shanghai, 200040, China; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
³ Department of Urology, Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
⁴ Department of Pathology, Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
⁵ Department of Urology, Tenth People's Hospital, Tongji University, Shanghai, 200072, China. Electronic address: yaoxudong67@sina.com.

PMID: 28209239
DOI: 10.1016/j.ejso.2017.01.013

Abstract

Background: Previous study has indicated association between REG1α and bladder cancer. The aim of this study was to investigate the role of Regenerating gene I alpha (REG1α) in bladder cancer.

Methods: The role of REG1α in bladder cancer cell proliferation, migration and VEGF-induced angiogenesis was explored in vitro and in vivo. Immunohistochemistry (IHC) analysis was assessed to determine the expression of REG1α in ten paired bladder cancer and adjacent non-cancerous tissues, and in 296 bladder cancer samples.

Results: Down-regulation of REG1α expression significantly reduced the proliferation, migration, invasion and VEGF-induced angiogenesis in vitro and the growth of xenograft tumors in vivo. VEGF expression in bladder cancer is associated with REG1α expression and recurrence. REG1α was overexpressed in bladder cancer tissues compared with adjacent normal samples. Patients with elevated REG1α exhibited shorter recurrence times and poor survival.

Conclusion: Downregulation of REG1α expression can reduce tumor growth, migration, invasion and angiogenesis. Our study demonstrates that REG1α can be used as a marker of recurrence and prognosis in bladder cancer. Therefore, REG1α targeting in bladder cancer patients represents a promising therapeutic strategy.

Keywords: Angiogenesis; Bladder cancer; REG1α; Urothelial carcinoma; VEGF.

MeSH terms

Animals
Blotting, Western
Carcinoma, Transitional Cell / metabolism*
Carcinoma, Transitional Cell / pathology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Down-Regulation
Gene Expression Regulation, Neoplastic*
Humans
Immunohistochemistry
In Vitro Techniques
Lithostathine / metabolism*
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Transplantation
Neovascularization, Pathologic / metabolism*
RNA Interference
Random Allocation
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology
Vascular Endothelial Growth Factor A / metabolism*

Substances

Lithostathine
REG1A protein, human
VEGFA protein, human
Vascular Endothelial Growth Factor A