Integration of zebrafish fin regeneration genes with expression data of human tumors in silico uncovers potential novel melanoma markers.
Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer. We therefore undertook a systematic gene expression study to identify genes upregulated during the re-growth of caudal fin tissue. By applying a high stringency cut-off value of 4-fold change, we identified 54 annotated genes significantly overexpressed in regenerating blastema. Further bioinformatics data mining studies showed that 22 out of the 54 regeneration genes where overexpressed in melanoma compared to normal skin or other cancers. Whereas the role of TNC (tenascin C) and FN1 (fibronectin 1) in melanoma development is well documented, implication of MARCKS, RCN3, BAMBI, PEA3/ETV4 and the FK506 family members FKBP7, FKBP10 and FKBP11 in melanoma progression is unclear. Corresponding proteins were detected in melanoma tissue but not in normal skin. High expression of FKBP7, DPYSL5 and MDK was significantly associated with poor survival. We discuss a potential role of these novel melanoma genes, which have promising potential as new therapeutic targets or diagnostic markers.
University of Bordeaux, Talence F-33405, France.|INSERM, LAMC, U1029, Talence F-33405, France.|INSERM, BMGIC, U1035, Bordeaux F-33000, France.
Martin
M
Hagedorn
University of Bordeaux, Talence F-33405, France.|INSERM, LAMC, U1029, Talence F-33405, France.
Géraldine
G
Siegfried
University of Bordeaux, Talence F-33405, France.|INSERM, BMGIC, U1035, Bordeaux F-33000, France.
Katarzyna B
KB
Hooks
University of Bordeaux, Talence F-33405, France.|INSERM, LAMC, U1029, Talence F-33405, France.
Abdel-Majid
AM
Khatib
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058500:Animal Fins / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D006867:Hydrolases; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D015027:Zebrafish / Q000235:genetics*
C485671:BAMBI protein, human; D002135:Calcium-Binding Proteins; C000592090:FKBP7 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C415087:DPYSL5 protein, human; D006867:Hydrolases; D022021:Tacrolimus Binding Proteins; C110054:FKBP10 protein, human
BAMBI; FK506-binding proteins; angiogenesis; melanoma; regeneration
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