| First Author | Kiguchi K | Year | 1997 |
| Journal | J Invest Dermatol | Volume | 108 |
| Issue | 5 | Pages | 784-91 |
| PubMed ID | 9129233 | Mgi Jnum | J:40006 |
| Mgi Id | MGI:87345 | Doi | 10.1111/1523-1747.ep12292237 |
| Citation | Kiguchi K, et al. (1997) Analysis of the ability of 12-O-tetradecanoylphorbol-13-acetate to induce epidermal hyperplasia, transforming growth factor-alpha, and skin tumor promotion in wa-1 mice. J Invest Dermatol 108(5):784-91 |
| abstractText | Wa-1 mutant mice possess a defect in the production of transforming growth factor-alpha (TGF-alpha) that leads to a phenotype characterized by wavy hair and curly whiskers, In light of recent evidence indicating the importance of TGF-alpha in epithelial tumorigenesis, this study characterizes the responsiveness of wa-l mice to skin tumor promotion by the phorbol ester, 12-O- tetradecanoylphorbol-13-acetate (TPA). The responsiveness of wa-l mice to TPA was compared with that of SENCAR and C57BL/6 mice, representing mouse lines highly sensitive and resistant to skin tumor promotion, respectively, Wa-l mice were found to be very resistant to skin tumor promotion by TPA after initiation with 10 nmol DMBA, similar to C57BL/6 mice, TPA failed to induce a dramatic increase in TGF-alpha mRNA and protein in the skin of wa-l mice, whereas TGF-alpha mRNA and protein were dramatically induced in the skin (both epidermis and dermis) of SENCAR and C57BL/6 mice. TPA treatment dramatically increased mRNA levels of two other EGF receptor ligands, amphiregulin and heparin binding-EGF, however, in the skin of all three mouse lines, Comparison of histologic changes in skin revealed that wa-l mice exhibited only modest sustained epidermal hyperplasia after multiple treatments with TPA, similar in magnitude to that of C57BL/6 mice and significantly lower than that of SENCAR mice, The current data indicate that wa-l mice are relatively resistant to TPA promotion. Possible mechanisms for this resistance are discussed. |
