Morgan et al. BMC Cancer 2010, 10:89 http://www.biomedcentral.com/1471-2407/10/89 R E S E A R C H A R T I C L E Open Access Targeting HOX and PBX transcription factors in ovarian cancer Richard Morgan1*, Lynn Plowright1, Kevin J Harrington2, Agnieszka Michael1, Hardev S Pandha1 Abstract Backgound: Ovarian cancer still has a relatively poor prognosis due to the frequent occurrence of drug resistance, making the identification of new therapeutic targets an important goal. We have studied the role of HOX genes in the survival and proliferation of ovarian cancer cells. These are a family of homeodomain-containing transcription factors that determine cell and tissue identity in the early embryo, and have an anti-apoptotic role in a number of malignancies including lung and renal cancer. Methods: We used QPCR to determine HOX gene expression in normal ovary and in the ovarian cancer cell lines SK-OV3 and OV-90. We used a short peptide, HXR9, to disrupt the formation of HOX/PBX dimers and alter transcriptional regulation by HOX proteins. Results: In this study we show that the ovarian cancer derived line SK-OV3, but not OV-90, exhibits highly dysregulated expression of members of the HOX gene family. Disrupting the interaction between HOX proteins and their co-factor PBX induces apoptosis in SK-OV3 cells and retards tumour growth in vivo. Conclusion: HOX/PBX binding is a potential target in ovarian cancer Background Ovarian cancer is a relatively uncommon malignancy, accounting for 4% of all cancers in the western world and 5% of all cancer deaths in women, but the mortality from this disease has improved little in the last 30 years [1]. Detection of ovarian cancer is often at a relatively advanced stage of the disease due to a lack of specific symptoms, and the overall survival for women diagnosed with stage III or IV ovarian cancer varies from 18.6- 46.7%. Treatment is usually a combination of surgery and chemotherapy, frequently using carboplatin, but recurrence and resistance is commonly observed with an associated high mortality in these cases [1]. In a similar manner to other cancers, ovarian cancers are known to over express a number of genes involved in early development. These include the HOX genes, a family of homeodomain-containing transcription factors that define the identity of cells and tissues during early development [2]. There are 39 HOX genes in mammals, divided into four groups (A-D) in tightly linked clusters on different chromosomes [3]. Whilst some HOX genes * Correspondence: r.morgan@surrey.ac.uk 1Postgraduate Medical School, University of Surrey, Guildford, UK have distinct functions in specific contexts, many others have overlapping or redundant functions during early development [4], in haematological malignancies [5], and in a number of other cancers including melanoma [6] and renal cancer [7], where the HOX genes have a potent anti-apoptotic function. This redundancy in HOX function is based in part upon the binding of similar DNA sequences, and also on the interaction of HOX proteins with a common set of co-factors includ- ing PBX. PBX modifies the DNA binding specificity of HOX proteins, influences the regulation of transcription, and is required for many aspects of HOX function [8]. Changes in HOX gene expression have also been observed in ovarian cancer [9-11]. Over expression of HOXA9, HOXA10 or HOXA11 results in a serous, endo- metrioid-like or mucinous-like phenotype respectively [9]. In addition, HOX genes have been shown to influ- ence the ability of ovarian cancer cells to invade other tissues [11], and to promote tumour growth [10]. In this study we have addressed whether HOX genes have an anti-apoptotic effect in ovarian cancer. We show that HOX expression in the ovarian cancer cell line SK-OV3 is highly dysregulated compared to normal ovarian tis- sue. Furthermore, interfering with HOX function using © 2010 Morgan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.