Data from Alterations of the Tumor Suppressor Gene <i>ARLTS1</i> in Ovarian Cancer

Abstract

<div>Abstract<p><i>ARLTS1</i> is a tumor suppressor gene initially described as a low-penetrance cancer gene: a truncated Trp149Stop (MUT) polymorphism is associated with general familial cancer aggregation and, particularly, high-risk familial breast cancer. DNA hypermethylation has been identified as a mechanism of <i>ARLTS1</i> expression down-regulation in lung carcinomas and B-cell chronic lymphocytic leukemia. We found that, in the majority of ovarian carcinomas (61.5%) and in a significant proportion of ovarian and breast cancer cell lines (45%), <i>ARLTS1</i> is strongly down-regulated due to DNA methylation in its promoter region. After <i>ARLTS1</i> restoration by adenoviral transduction, only the negative TOV-112 and the homozygously mutated (MUT) MCF7 cells, but not the OV-90 cells expressing a normal <i>ARLTS1</i> product, underwent apoptosis and inhibition of cell growth. Furthermore, <i>ARLTS1</i> reexpression significantly reduced the tumorigenic potential of TOV-112 in nude mice. On the contrary, the <i>ARLTS1</i>-MUT induced significantly lower levels of apoptosis in infected cells and reduced <i>in vivo</i> tumorigenesis only partially, supporting the hypothesis that Trp149Stop polymorphism is retained in the general population and predisposes to cancer because of a reduction, but not full loss, of normal <i>ARLTS1</i> function. (Cancer Res 2006; 66(21): 10287-91)</p></div>