Snail-regulated genes in malignant melanoma.
The demonstration that zinc-finger transcriptional repressors can control E-cadherin expression in epithelial cells has provided a new avenue of research in the field of epithelial-mesenchymal transition (EMT). One of these zinc-finger molecules is the transcription factor Snail, which controls gastrulation and neural crest EMT in different species. Additionally, Snail is involved in the development of malignant melanoma where a dramatic change in E-cadherin expression is an important early step for melanoma progression. For this study, a human cancer cDNA array was used which includes genes involved in cancer development and progression. Using the array we compared the gene expression pattern of the melanoma cell line Mel Im with a Mel Im cell clone stable transfected with antisense (as) SNAIL cDNA. We validated the significant differences of the expression of genes on mRNA level. Primarily, we observed changes in the expression of genes involved in EMT. Quantitative real-time polymerase chain reaction showed a down-regulation of MMP-2, EMMPRIN, SPARC, TIMP-1, t-PA, RhoA and Notch4 expression and a re-induction of E-cadherin expression in the as Snail cell clones. Furthermore, we measured the expression of integrin beta3, NM23b and RhoB. Additionally, we investigated whether the selected genes are influenced only through Snail or if E-cadherin can influence the expression of these genes. In summary, all examined genes which are influenced through Snail have a regulatory function in EMT processes as does Snail itself. The Snail target gene E-cadherin has no regulatory function with respect to the selected genes.
Kuphal
Silke
S
Institute of Pathology, University of Regensburg, D-93053 Regensburg, Germany.
Palm
Hans G
HG
Poser
Ina
I
Bosserhoff
Anja K
AK
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism*; D002999:Clone Cells; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D015820:Cadherins; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D010959:Tissue Plasminogen Activator; D020778:Matrix Metalloproteinase 2