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Title 

LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastric cancer

Authors 

Mi-rang KimJeong Hwan KimHay Ran JangHwan Mook KimChang Woo LeeS M NohK S SongJ S ChoH Y JeongY HahnYoung Il YeomHyang Sook YooYong Sung Kim

Publisher 

American Association for Cancer Research

Issue Date 

2008

Citation 

Cancer Research, vol. 68, no. 17, pp. 7147-7155

Keywords 

leucine rich repeat containing protein 3btumor suppressor proteinunclassified drugLRRC3B proteintumor proteinhydroxamic acidprimer DNADNA methylationgene silencinggenetic transfection

Abstract 

Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of LRRC3B, but treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased LRRC3B expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that LRRC3B expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that LRRC3B was significantly hypermethylated in gastric tumors. Stable transfection of LRRC3B in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and LRRC3B expression suppressed tumorigenesis in nude mice. Microarray analysis of LRRC3B-expressing xenograft tumors showed induction of immune response-related genes and IFN signaling genes. H&E-stained sections of LRRC3B-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that LRRC3B is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that LRRC3B silencing in cancer may play an important role in tumor escape from immune surveillance.

ISSN 

0008-5472

Link 

http://dx.doi.org/10.1158/0008-5472.CAN-08-0667

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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