Data from <b><i>Lysyl Oxidase</i></b> Is a Tumor Suppressor Gene Inactivated by Methylation and Loss of Heterozygosity in Human Gastric Cancers

Abstract

<div>Abstract<p><i>Lysyl oxidase</i> (<i>LOX</i>) and <i>HRAS-like suppressor</i> (<i>HRASLS</i>) are silenced in human gastric cancers and are reported to have growth-suppressive activities in <i>ras</i>-transformed mouse/rat fibroblasts. Here, we analyzed whether or not <i>LOX</i> and <i>HRASLS</i> are tumor suppressor genes in human gastric cancers. Loss of heterozygosity and promoter methylation of <i>LOX</i> were detected in 33% (9 of 27) and 27% (26 of 96) of gastric cancers, respectively. Biallelic methylation and loss of heterozygosity with promoter methylation were also demonstrated in gastric cancers. Silencing of <i>LOX</i> was also observed in colon, lung, and ovarian cancer cell lines. As for mutations, only one possible somatic mutation was found by analysis of 96 gastric cancer samples and 58 gastric and other cancer cell lines. When <i>LOX</i> was introduced into a gastric cancer cell line, MKN28, in which <i>LOX</i> and <i>HRASLS</i> were silenced, it reduced the number of anchorage-dependent colonies to 57 to 61%, and the number of anchorage-independent colonies to 11 to 23%. Sizes of tumors formed in nude mice were reduced to 19 to 26%. Growth suppression in soft agar assay was also observed in another gastric cancer cell line, KATOIII. On the other hand, neither loss of heterozygosity nor a somatic mutation was detected in <i>HRASLS</i>, and its introduction into MKN28 did not suppress the growth <i>in vitro</i> or <i>in vivo</i>. These data showed that <i>LOX</i> is a tumor suppressor gene inactivated by methylation and loss of heterozygosity in gastric cancers, and possibly also in other cancers.</p></div>