Latexin is downregulated in human upper digestive track tumors and exhibits tumor suppressor potential

ABSTRACT: Latexin (Lxn) was originally isolated as a tissue specific marker of rat neuron. It is expressed in various tissues of humans and many other vertebrates. Lxn inhibits human carboxypeptidase A4 (hCPA4), whose expression is induced by histone deacetylase inhibitors in prostate cancer cells, and is associated with cancer progression. Structural analysis has shown significant similarity between Lxn protein and the tumor suppressor protein TIG1. Recent reports have demonstrated Lxn functions in the negative control of hematopoietic stem cell numbers (HSC) in mice. In the present study, an anti-Lxn monoclonal antibody 1G11 was generated and Western blot analysis showed that Lxn was expressed mainly in the cytoplasm of numerous human cell lines. Immunohistochemical analysis in gastric cancer tissues and the corresponding adjacent normal tissues showed that Lxn expression was lower in cancer tissues as compared to normal tissues. In addition, the Lxn gene was exogenously introduced into a Lxn null gastric cancer cell line, MGC803. Results of colony formation assay, soft agar assay and tumor growth in nude mice showed that over-expression of Lxn inhibits the proliferation and tumorigenicity of MGC803 cells expressing Lxn. Thirty-seven genes, whose expression were altered in response to Lxn expression were identified by microarray analysis. Methylation analysis of the central promoter region of the Lxn gene in several cell lines suggested that Lxn expression was silenced by CpG hypermethylation. Taken together, our results indicate that Lxn is a potential tumor suppressor and plays a role in negative control of tumor cell growth.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15787 | GEO | 2011/04/14

SECONDARY ACCESSION(S): PRJNA116865

REPOSITORIES: GEO