title: Functional and prognostic relevance of the homeobox protein MSX2 in malignant melanoma.
abstract: BACKGROUND
  The homeobox containing transcription factor MSX2 is a key regulator of embryonic development and has been implicated to have a role in breast and pancreatic cancer.
  
  
  METHODS
  Using a selection of two- and three-dimensional in vitro assays and tissue microarrays (TMAs), the clinical and functional relevance of MSX2 in malignant melanoma was explored. A doxycyline-inducible over-expression system was applied to study the relevance of MSX2 in vitro. For TMA construction, tumour material from 218 melanoma patients was used.
  
  
  RESULTS
  Ectopic expression of MSX2 resulted in the induction of apoptosis and reduced the invasive capacity of melanoma cells in three-dimensional culture. MSX2 over-expression was shown to affect several signalling pathways associated with cell invasion and survival. Downregulation of N-Cadherin, induction of p21 and inhibition of both BCL2 and Survivin were observed. Cytoplasmic MSX2 expression was found to correlate significantly with increased recurrence-free survival (P=0.008). Nuclear expression of MSX2 did not result in significant survival correlations, suggesting that the beneficial effect of MSX2 may be independent of its DNA binding activity.
  
  
  CONCLUSIONS
  MSX2 may be an important regulator of melanoma cell invasion and survival. Cytoplasmic expression of the protein was identified as biomarker for good prognosis in malignant melanoma patients.
authors: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
authors: G
authors: G
authors: Gremel
authors: D
authors: D
authors: Ryan
authors: M
authors: M
authors: Rafferty
authors: F
authors: F
authors: Lanigan
authors: S
authors: S
authors: Hegarty
authors: M
authors: M
authors: Lavelle
authors: I
authors: I
authors: Murphy
authors: L
authors: L
authors: Unwin
authors: C
authors: C
authors: Joyce
authors: W
authors: W
authors: Faller
authors: E W
authors: EW
authors: McDermott
authors: K
authors: K
authors: Sheahan
authors: F
authors: F
authors: Ponten
authors: W M
authors: WM
authors: Gallagher
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D040081:Protein Array Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018874:Spheroids, Cellular; D016019:Survival Analysis; D000077022:Survivin; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C107489:BIRC5 protein, human; C050361:CDH2 protein, human; C493956:CDKN1A protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; D051034:Inhibitor of Apoptosis Proteins; C084119:MSX2 protein; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin