Proteinase-activated receptor-2 (PAR2): a tumor suppressor in skin carcinogenesis.
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).
Rattenholl
Anke
A
Department of Dermatology and Interdisciplinary Center for Clinical Research IZKF Münster, University of Münster, Münster, Germany.
Seeliger
Stephan
S
Buddenkotte
Jörg
J
Schön
Margarete
M
Schön
Michael P
MP
Ständer
Sonja
S
Vergnolle
Nathalie
N
Steinhoff
Martin
M
D000818:Animals; D045744:Cell Line, Tumor; D004817:Epidermis / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D044464:Receptor, PAR-2 / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D044464:Receptor, PAR-2; D053773:Transforming Growth Factor beta1