Targeting HOX and PBX transcription factors in ovarian cancer.
BACKGROUND
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.


CONCLUSIONS
HOX/PBX binding is a potential target in ovarian cancer.
Morgan
Richard
R
Postgraduate Medical School, University of Surrey, Guildford, UK. r.morgan@surrey.ac.uk
Plowright
Lynn
L
Harrington
Kevin J
KJ
Michael
Agnieszka
A
Pandha
Hardev S
HS
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D019281:Dimerization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
D004268:DNA-Binding Proteins; C489126:HOXB5 protein, human; C489493:HOXD11 protein, human; C088822:HOXD9 protein, human; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; C083400:PBX1 protein, human