Stromelysin-1 and mesothelin are differentially regulated by Wnt-5a and Wnt-1 in C57mg mouse mammary epithelial cells.
BACKGROUND
The Wnt signal transduction pathway is important in a wide variety of developmental processes as well as in the genesis of human cancer. Vertebrate Wnt pathways can be functionally separated into two classes, the canonical Wnt/beta-catenin pathway and the non-canonical Wnt/Ca2+ pathway. Supporting differences in Wnt signaling, gain of function of Wnt-1 in C57mg mouse mammary epithelial cells leads to their morphological transformation while loss of function of Wnt-5a leads to the same transformation. Many downstream target genes of the Wnt/beta-catenin pathway have been identified. In contrast, little is known about the Wnt/Ca2+ pathway and whether it regulates gene expression.


RESULTS
To test the hypothesis that a specific cell line can respond to distinct Wnts with different patterns of gene expression, we over-expressed Wnt-5a and Rfz-2 in C57mg mammary epithelial cells and compared this cell line to C57mg cells over-expressing Wnt-1. These Wnts were chosen since previous studies suggest that C57mg cells respond differently to these Wnts, and since these Wnts can activate different signaling pathways in other systems. Using DNA microarray analysis, we identified several genes that are regulated by Wnt-5a and Rfz-2 as well as by Wnt-1. We then focused on two genes previously linked to various cancers, mesothelin and stromelysin-1, which are respectively up-regulated by Wnt-1 and Wnt-5a in C57mg cells.


CONCLUSIONS
Different Wnts have distinct effects on gene expression in a single cell line.
Prieve
Mary G
MG
Department of Pharmacology, Howard Hughes Medical Institute, and Center for Developmental Biology, University of Washington School of Medicine, Seattle, WA 98195, USA. mgprieve@u.washington.edu
Moon
Randall T
RT
D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008321:Mammary Glands, Animal / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D000090204:Mesothelin; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715528:Msln protein, mouse; D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C438615:Wnt5a protein, mouse; D029961:Zebrafish Proteins; D019278:Matrix Metalloproteinase 3; D000090204:Mesothelin