Melanoma metastasis is associated with enhanced expression of the syntenin gene.
Primary cutaneous melanomas and melanoma metastases were examined for differential gene expression using subtractive suppression hybridization in a search for any genes associated with metastasis. Generating a subtracted library of candidate genes up-regulated in melanoma metastases, this library contained 8 different cDNAs, among them a cDNA fragment of the syntenin gene which was overexpressed in further independent melanoma resection specimens on cDNA Southern blots when compared to acquired melanocytic nevi from which melanomas are known to arise. Upon immunohistochemistry, the syntenin protein expression was detected in the cytoplasm of primary cutaneous melanomas and melanoma metastases. Melanoma metastases exhibited higher proportions of tumour cells positive for syntenin immunostaining in comparison to acquired melanocytic nevi or non-metastasizing primary melanomas which was statistically significant. In addition to melanoma, gastric cancer tissues exhibited a higher syntenin mRNA expression on a matched tumour/normal cDNA array than their normal counterparts which was statistically significant. Altogether, we here first describe the detection of the syntenin protein in resection specimens of melanocytic lesions. We conclude that melanoma metastasis is associated with increased expression of the syntenin gene which may participate in signal transduction and cell adhesion via the multifunctional protein-binding properties of its tandem PDZ domains.
Helmke
Burkhard M
BM
Department of Pathology, Heidelberg University Clinics, D-69120 Heidelberg, Germany.
Polychronidis
Myriam
M
Benner
Axel
A
Thome
Marianne
M
Arribas
Joaquín
J
Deichmann
Martin
M
D015152:Blotting, Northern; D015139:Blotting, Southern; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009362:Neoplasm Metastasis; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D053676:Syntenins; D014158:Transcription, Genetic; D015854:Up-Regulation
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C109621:SDCBP protein, human; D053676:Syntenins; D012313:RNA