B184
HOX transcription factors as potential therapeutic targets in non-small cell lung cancer
Lynn Plowright1, Kevin Harrington2, Hardev Pandha1, Richard Morgan1
1University of Surrey, Guildford, Surrey, UK, 2The Institute of Cancer Research, London, UK
Background
The HOX genes are a family of homeodomain-containing transcription factors that determine the identity of cells and tissues during embryonic development. They are also known to behave as oncogenes in some haematological malignancies. The focus of this study is on the role of HOX genes in non-small cell lung cancer.
Method
HOX expression in normal lung tissue, non-small cell lung tumours and the derived cell lines A549 and H23 were determined by QPCR. HOX function was blocked by treating cells with the HXR9 peptide, which has been shown to block HOX / PBX binding.
Results
The expression of many of the HOX genes is highly elevated in primary non-small cell lung cancers and in the derived cell lines A549 and H23. Furthermore, blocking the activity of HOX proteins by interfering with their binding to the PBX co-factor causes these cells to undergo apoptosis in vitro and reduces the growth of A549 tumours in vivo.
Conclusion
These findings suggest that the interaction between HOX and PBX proteins is a potential therapeutic target in non-small cell lung cancer.
