title: Pro-neural transcription factors as cancer markers.
abstract: BACKGROUND
  The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours.
  
  
  RESULTS
  Expression arrays were used to identify up-regulated transcripts in a neuroendocrine (NE) transgenic mouse model of prostate cancer. Amongst these were several genes normally expressed in neural tissues, including the pro-neural transcription factors Ascl1 and Hes6. Using quantitative RT-PCR and immuno-histochemistry we showed that these same genes were highly expressed in castrate resistant, metastatic LNCaP cell-lines. Finally we performed a meta-analysis on expression array datasets from human clinical material. The expression of these pro-neural transcripts effectively segregates metastatic from localised prostate cancer and benign tissue as well as sub-clustering a variety of other human cancers.
  
  
  CONCLUSIONS
  By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined. We suggest that the aberrant initiation of differentiation programs may confer a selective advantage on cells in all contexts and this approach to identify biomarkers therefore has the potential to uncover proteins equally applicable to pre-clinical and clinical cancer biology.
authors.affiliation: Uro-Oncology Research Group, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. maria.vias@cancer.org.uk
authors.forename: Maria
authors.initials: M
authors.lastname: Vias
authors.forename: Charlie E
authors.initials: CE
authors.lastname: Massie
authors.forename: Philip
authors.initials: P
authors.lastname: East
authors.forename: Helen
authors.initials: H
authors.lastname: Scott
authors.forename: Anne
authors.initials: A
authors.lastname: Warren
authors.forename: Zongxiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Alexander Yu
authors.initials: AY
authors.lastname: Nikitin
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Ian G
authors.initials: IG
authors.lastname: Mills