Morgan et al. BMC Cancer 2010, 10:89 http://www.biomedcentral.com/1471-2407/10/89 investigation. Possible explanations may lie in the origi- nal expression of HOX genes in the embryonic cells, in which case the HOX expression profile would influence the phenotype of each cancer. There is clear evidence for this in ovarian cancer where the expression of HOXA9, HOXA10 or HOXA11 confer a serous, endome- trioid-like and mucinous-like phenotype respectively [9]. It is also clear that the over-expression of some HOX genes is directly related to the degree of malignancy, for example elevated expression of HOXC8 is correlated with the loss of differentiation of prostate tumours [20], although our data indicate that HOXC8 is actually expressed at a lower level in the ovarian cancer lines SK-OV3 and OV-90 as compared to normal ovarian tis- sue. In addition, loss of HOXA5 and HOXA9 expression is generally associated with an increased resistance to apoptosis and tumour survival [22], although both of these genes are expressed at relatively high levels in SK- OV3 compared to normal ovarian tissue and OV-90. However, recent studies have shown that HOXA9 expression increases considerably in advanced stages of ovarian cancer, indicating that it may have a different function as the disease progresses [23]. The other HOX genes that are notably upregulated in SK-OV3 cells (but generally not OV-90 cells) have previously been shown to be upregulated in other cancers, including HOXA13 [24], HOXB5 [23], HOXB9 [25] and HOXD9 [26]. One difficulty in interpreting this data is that, in gen- eral, there is a high level of redundancy in HOX func- tion which may mask the contribution of any of these individual genes to a malignant phenotype. Hence a post-translational approach may reveal more about glo- bal HOX functions in cancer. The HXR9 peptide blocks the binding of HOX proteins to their PBX co-factor and in doing so alters the way in which they bind to DNA and hence changes the regulation of their target genes [6,7]. HXR9 causes melanoma and renal cancer cells to undergo apoptosis, and here we have shown that the SK-OV3 cell line derived from an ovarian tumour responds in the same way, indicating that the HOX/ PBX interaction is a potential target in ovarian cancer therapy. Interestingly, HXR9 does not induce cell death in OV-90 cells that generally do not show dysregulated HOX expression. The role of HOX genes in early development is highly conserved [2]. They may also have a common role in malignant cells, as evidenced by a common sensitivity to HXR9 and in similar transcriptional responses, including the upregulation of cFos. This change in cFos expression was previously shown to be responsible, at least in part, for the induction of apoptosis [6]. Recent studies have shown that cFos transcriptionally represses the key anti- apoptotic gene c-FLIP(L), greatly sensitising prostate cancer cells to TRAIL-induced apoptosis [27,28]. Page 8 of 9 Conclusions Novel targets are needed in ovarian cancer therapy as the long term survival of patients is poor despite the trial of numerous chemotherapeutic regimes including the current standard of care, carboplatin/paclitaxel [1,29]. The HOX genes are independent of the targets of current chemotherapeutics (as far as this can be known), and hence targeting the HOX/PBX interaction is a potential alternative or addition to current therapeu- tics when drug resistance develops. Author details 1Postgraduate Medical School, University of Surrey, Guildford, UK. 2Targeted Therapy Team, Chester Beatty Laboratories, The Institute of Cancer Research, London, UK. Authors’ contributions All authors have read and approved the final manuscript. The authors made the following contributions to this work: LP conducted lab based experimental work, KJH was involved in experimental design and critique, AM was in charge of sample acquisition and critique, HSP helped to write the manuscript and RM was involved in experimental design and also wrote the manuscript. All authors read and approved the final paper. Competing interests The authors declare that they have no competing interests. Received: 11 March 2009 Accepted: 10 March 2010 Published: 10 March 2010 References 1. Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U: Carcinoma of the ovary. FIGO 6th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006, 95(Suppl 1):S161-92. 2. Iimura T, Pourquié O: Hox genes in time and space during vertebrate body formation. Dev Growth Differ 2007, 49:265-75. 3. Hoegg S, Meyer A: Hox clusters as models for vertebrate genome evolution. Trends Genet 2005, 21:421-424. 4. McIntyre DC, Rakshit S, Yallowitz AR, Loken L, Jeannotte L, Capecchi MR, Wellik DM: Hox patterning of the vertebrate rib cage. Development 2007, 134:2981-2989. 5. Eklund EA: The role of HOX genes in malignant myeloid disease. Curr Opin Hematol 2007, 14:85-89. 6. Morgan R, Pirard P, Shears L, Sohal S, Pettengell R, Pandha HS: Antagonism of HOX/PBX dimer formation blocks the in vivo proliferation of melanoma. Cancer Res 2007, 67:5806-13. 7. Shears L, Plowright L, Harrington K, Pandha HS, Morgan R: Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P. J Urol 2008, 180(5): N2196-201. 8. Moens CB, Selleri L: Hox cofactors in vertebrate development. Dev Biol 2006, 291:193-206. 9. Cheng W, Liu J, Yoshida H, Rosen D, Naora H: Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med 2005, 5:531-7. 10. Miao J, Wang Z, Provencher H, Muir B, Dahiya S, Carney E, Leong CO, Sgroi DC, Orsulic S: HOXB13 promotes ovarian cancer progression. Proc Natl Acad Sci USA 2007, 104:17093-8. 11. Yamashita T, Tazawa S, Yawei Z, Katayama H, Kato Y, Nishiwaki K, Yokohama Y, Ishikawa M: Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells. Int J Oncol 2006, 28:931-8. 12. Workman P, Twentyman P, Balkwill F, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T, Wallace J: United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR)