Data from <i>LRRC3B</i>, Encoding a Leucine-Rich Repeat-Containing Protein, Is a Putative Tumor Suppressor Gene in Gastric Cancer

Abstract

<div>Abstract<p>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 <i>LRRC3B</i> was aberrantly methylated in gastric cancer. Gastric cancer cell lines displayed epigenetic silencing of <i>LRRC3B</i>, but treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine and/or the histone deacetylase inhibitor trichostatin A increased <i>LRRC3B</i> expression in gastric cancer cell lines. Real-time reverse transcription-PCR analysis of 96 paired primary gastric tumors and normal adjacent tissues showed that <i>LRRC3B</i> expression was reduced in 88.5% of gastric tumors compared with normal adjacent tissues. Pyrosequencing analysis of the promoter region revealed that <i>LRRC3B</i> was significantly hypermethylated in gastric tumors. Stable transfection of <i>LRRC3B</i> in SNU-601 cells, a gastric cancer cell line, inhibited anchorage-dependent and anchorage-independent colony formation, and <i>LRRC3B</i> expression suppressed tumorigenesis in nude mice. Microarray analysis of <i>LRRC3B</i>-expressing xenograft tumors showed induction of immune response–related genes and IFN signaling genes. H&E-stained sections of <i>LRRC3B</i>-expressing xenograft tumors showed lymphocyte infiltration in the region. We suggest that <i>LRRC3B</i> is a putative tumor suppressor gene that is silenced in gastric cancers by epigenetic mechanisms and that <i>LRRC3B</i> silencing in cancer may play an important role in tumor escape from immune surveillance. [Cancer Res 2008;68(17):7147–55]</p></div>