University of Surrey Institute of Advanced Studies

University of Surrey

Transcription factors as targets and markers in cancer

23rd April 2007

Workshop Report

The fields of transcriptional control and cancer are both vast, but this meeting was the first of its kind in specifically addressing how the former could be used as a therapeutic and diagnostic strategy in the latter. On the day there was a great turn out with around 80 delegates and there were a number of lively discussions.

The papers

Dr Yvonne Olsson (Lund University, Sweden) began the day with her paper entitled 'E2F in prostate cancer '. E2F is a key regulator of the cell cycle and is therefore an important target in cancer therapy. Dr Olsson described its complex regulatory relationships with other genes and how this could further our understanding of the biology of this protein.

The next three papers all concerned the role of HOX genes in cancer. The HOX genes are key determinates of cell and tissue identity in early embryogenesis and are also upregulated in many different types of tumour. Professor Clemente Cillo, University Medical School, Naples presented 'HOX genes and human cancers: a link between development, evolution and pathology'. Prof Cillo described how different combinations of HOX genes are expressed in different types of cancer, and how this may represent a possible diagnostic and prognostic tool. Thus for example HOXA13 is highly expressed in most liver cancers whilst HOXC6 is associated with prostatic cancer. Continuing this theme, Dr Richard Morgan (Postgraduate Medical School, University of Surrey) discussed the role of HOX genes in development and disease. He described a method of blocking HOX gene function in cancer cells by stopping their interaction with other proteins. This kills cancer cells in a highly specific manner and presents a promising target for cancer therapy (this work is going to appear in the journal Cancer Research this month). Professor Hannes Klump (Hanover University, Germany) presented 'HOXB4 in stem cell renewal and proliferation.' The HOXB4 transcription factor is known to promote the proliferation of blood stem cells and so may be useful in culturing these cells prior to transplant. Prof Klump provided some important results showing that HOXB4 expression can eventually cause benign myeloproliferation and therefore may not be as clinically useful as hoped.

The other papers of the workshop addressed a variety of other transcription factors but they all provided important insights into the molecular biology of cancer. Professor Helen Hurst (Queen Mary's, University Hospital, London) presented 'AP- 2 transcription factors in breast cancer'. The AP-2 gene family consists of five transcription factors each of which can act as both repressors and activators of transcription. Prof Hurst has shown that one member, AP-2γ, regulates cancer cell survival by blocking p53 activation of the p21CIP gene. High levels of AP-2γ are associated with a poor prognosis in breast cancer.

A further transcription factor that promotes cell survival is FOXO. Professor Eric W-F Lam (Imperial College, London) discussed 'FOXO transcription factors —regulators of cell fate and drug resistance'. Prof Lam provided some fascinating insights on his work with the FOXO family of transcription factors. FOXO proteins can promote the expression of proteins involved in drug resistance and also block programmed cell death and may therefore protect cancer cells from chemotherapeutic drugs.

The meeting helped emphasise the importance of transcriptional control in cancer therapeutics and diagnostics, and helped identify a number of key areas where different research groups could interact. It is also made more apparent the enormous complexity of cancer biology.

Workshop Themes

The main themes to emerge were (i) the overlap in function of different transcription factors, (ii) the potential for different combinations of transcription factors to define specific types of cancer and (iii) the potential of targeting transcription factors in therapeutics.

Next Steps

It was agreed that:

  1. A further seminar should be held in 2008 to review progress
  2. The speakers are to explore the possibility of using their papers to form the basis of a book seeking to act as a comprehensive review of this field.

Dr Richard Morgan

17 June, 2007