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Background  The  HOX  genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys-regulated in some cancers. In this study we examined the expression and oncogenic function of  HOX  genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos.    Methods  We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co-factor. Apoptosis was measured using a FACS-based assay with Annexin, and  HOX  gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model.    Results  We show that  HOX  genes are significantly dysregulated in malignant mesothelioma. Targeting  HOX  genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of  HOX  genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of  HOX  expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of  HOXB4  is strongly associated with overall survival.    Conclusion   HOX  genes are a potential therapeutic target in mesothelioma, and  HOXB4  expression correlates with overall survival.

HOX transcription factors are potential targets and markers in malignant mesothelioma