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Publication : Proteinase-activated receptor-2 (PAR2): a tumor suppressor in skin carcinogenesis.

First Author  Rattenholl A Year  2007
Journal  J Invest Dermatol Volume  127
Issue  9 Pages  2245-52
PubMed ID  17476297 Mgi Jnum  J:123747
Mgi Id  MGI:3719495 Doi  10.1038/sj.jid.5700847
Citation  Rattenholl A, et al. (2007) Proteinase-activated receptor-2 (PAR2): a tumor suppressor in skin carcinogenesis. J Invest Dermatol 127(9):2245-52
abstractText  The proteinase-activated receptor PAR(2) has been demonstrated to modulate tumor growth, invasion and metastasis in various tissues. However, the role of PAR(2) in cutaneous cancerogenesis is still unknown. Here we could show a protective role of PAR(2) in the development of epidermal skin tumors: we established a mouse skin tumor model using chemically induced carcinogenesis. Tumors started to appear after eight weeks. After 13 weeks, PAR(2)-deficient mice showed a significantly increased number of skin tumors (14 per animal on the average) in contrast to the wild type (eight tumors per mouse). Analysis of possible signal transduction pathways activated upon PAR(2) stimulation in HaCaT keratinocytes showed an involvement of extracellular signal-regulated kinase 1/2 and profound epidermal growth factor receptor transactivation, leading to secretion of the tumor-suppressing factor transforming growth factor-beta1. Thus, our results provide early experimental evidence for a tumor-protective role of PAR(2).
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