| First Author | Oka M | Year | 2010 |
| Journal | Carcinogenesis | Volume | 31 |
| Issue | 10 | Pages | 1897-902 |
| PubMed ID | 20688835 | Mgi Jnum | J:164693 |
| Mgi Id | MGI:4834972 | Doi | 10.1093/carcin/bgq164 |
| Citation | Oka M, et al. (2010) Enhancement of ultraviolet B-induced skin tumor development in phospholipase Cepsilon-knockout mice is associated with decreased cell death. Carcinogenesis 31(10):1897-902 |
| abstractText | Phospholipase C (PLC) epsilon is a phosphoinositide-specific PLC regulated by small guanosine triphosphatases including Ras and Rap. Our previous studies revealed that PLCepsilon gene-knockout (PLCepsilon(-/-)) mice exhibit marked resistance to tumor formation in two-stage skin chemical carcinogenesis using 7,12-dimethylbenz(a)anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate as a promoter. In this model, PLCepsilon functions in tumor promotion through augmentation of 12-O-tetradecanoylphorbol-13-acetate-induced inflammation. In this study, we have further assessed the role of PLCepsilon in tumorigenesis using a mouse model of ultraviolet (UV) B-induced skin tumor development. We irradiated PLCepsilon(+/+), PLCepsilon(+/-) or PLCepsilon(-/-) mice with doses of UVB increasing from 1 to 10 kJ/m(2) three times a week for a total of 25 weeks and observed tumor formation for up to 50 weeks. In sharp contrast to the results from the two-stage chemical carcinogenesis study, PLCepsilon(-/-) mice developed a large number of neoplasms including malignant tumors, whereas PLCepsilon(+/+) and PLCepsilon(+/-) mice developed a relatively small number of benign tumors. However, UVB-induced skin inflammation was greatly suppressed in PLCepsilon(-/-) mice, as observed with 12-O-tetradecanoylphorbol-13-acetate-induced inflammation, implying that PLCepsilon's role in the suppression of UVB-induced tumorigenesis is not mediated by inflammation. Studies of the tumor initiation stage revealed that UVB-induced cell death in the skin was markedly suppressed in PLCepsilon(-/-)mice. Our findings identify a novel function for PLCepsilon as a critical molecule regulating UVB-induced cell death and suggest that resistance to UVB-induced cell death conferred by the absence of PLCepsilon is closely related to the higher incidence of skin tumor formation. |
