RASSF10 is epigenetically silenced and functions as a tumor suppressor in gastric cancer

Journal Article · Fri Mar 22 00:00:00 EDT 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.02.033· OSTI ID:22239523

Wei, Ziran ^[1]; Chen, Xia ^[2]; Chen, Ji; Wang, Weimin ^[1]; Xu, Xudong ^[2]; Cai, Qingping ^[1]

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1. Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai (China)
2. Urology Department, Minhang District Central Hospital, Shanghai (China)

Highlights: ► Epigenetic silencing of RASSF10 gene expression in GC cells. ► RASSF10 overexpression inhibits cell growth in vitro and in vivo. ► RASSF10 induces apoptosis in GC cells. ► RASSF10 inhibits Wnt/β-catenin signaling pathway. -- Abstract: Ras association domain family (RASSF) proteins are encoded by several tumor suppressor genes that are frequently silenced in human cancers. In this study, we investigated RASSF10 as a target of epigenetic inactivation and examined its functions as a tumor suppressor in gastric cancer. RASSF10 was silenced in six out of eight gastric cancer cell lines. Loss or downregulation of RASSF10 expression was associated with promoter hypermethylation, and could be restored by a demethylating agent. Overexpression of RASSF10 in gastric cancer cell lines (JRST, BGC823) suppressed cell growth and colony formation, and induced apoptosis, whereas RASSF10 depletion promoted cell growth. In xenograft animal experiments, RASSF10 overexpression effectively repressed tumor growth. Mechanistic investigations revealed that RASSF10 inhibited tumor growth by blocking activation of β-catenin and its downstream targets including c-Myc, cyclinD1, cyclinE1, peroxisome proliferator-activated receptor δ, transcription factor 4, transcription factor 1 and CD44. In conclusion, the results of this study provide insight into the role of RASSF10 as a novel functional tumor suppressor in gastric cancer through inhibition of the Wnt/β-catenin signaling pathway.

• OSTI ID: 22239523
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 432, Issue 4; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
APOPTOSIS
COLONY FORMATION
GENES
IN VITRO
IN VIVO
NEOPLASMS
POWER LOSSES
RECEPTORS
TRANSCRIPTION FACTORS