Targeting HOX and PBX transcription factors in ovarian cancer

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.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.HOX/PBX binding is a potential target in ovarian cancerOvarian 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 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