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New, tacky oncogenes
Genome Biologyvolume 3, Article number: spotlight-20020821-01 (2002)
The β and γ catenins both mediate cell-to-cell adhesion, with β catenin also being involved in a signal transduction cascade that promotes cell proliferation, but their role in tumorigenesis has been unclear. In the August 15 Genes & Development, Maralice Conacci-Sorrell and colleagues at The Weizmann Institute of Science, Rehovot, Israel, show that both β and γ catenins induce transcription of Nr-CAM (a neuronal cell adhesion molecule) and play a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility (Genes Dev 2002, 16:2058-2072).
Conacci-Sorrell et al. used DNA microarrays to analyze human carcinoma cell lines and observed that expression of Nr-CAM was dramatically increased by β and γ catenin. Nr-CAM expression in mouse fibroblast cells caused rapid proliferation in cell culture, and when these cells were injected into nude mice they produced rapidly developing tumors. In addition Conacci-Sorrell et al., showed that Nr-CAM is highly expressed in murine and human melanoma cells and human colon cancer tissue, but not in normal colon tissue and melanocytes.
Because Nr-CAM is a molecule expressed on the outer surface of cells, the team suggest that new anti-cancer therapies based on Nr-CAM targeting could be more effective than those that focus on molecules expressed inside the cell.
Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze'ev A: Nr-CAM is a target gene of the β-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.Genes Dev 2002, 16:2058-2072., [http://www.genesdev.org/cgi/content/abstract/16/16/2058]
The Weizmann Institute of Science, [http://www.weizmann.ac.il/]