Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.
We have generated a mouse strain lacking protein kinase C (PKC) eta to evaluate its significance in epithelial organization and tumor formation. The PKCeta-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. The tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCeta suppresses tumor promotion. Epidermal hyperplasia induced by topical TPA treatment was prolonged in the mutant mice. The enhanced tumor formation may be closely associated with the prolonged hyperplasia induced by topical TPA treatment. In the mutant mice, after inflicting injury by punch biopsy, wound healing on the dorsal skin, particularly reepithelialization, was significantly delayed and impaired in structure. Impairment of epithelial regeneration in wound healing indicates a possibility that PKCeta plays a role in maintenance of epithelial architecture. Homeostasis in epithelial tissues mediated by PKCeta is important for tumor formation in vivo. We propose that PKCeta is involved in tumor formation modulated by regulation of proliferation and remodeling of epithelial cells in vivo.
Chida
Kazuhiro
K
Department of Animal Resource Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan. acchida@mail.ecc.u-tokyo.ac.jp
Hara
Takeshi
T
Hirai
Takaaki
T
Konishi
Chieko
C
Nakamura
Kenji
K
Nakao
Kazuki
K
Aiba
Atsu
A
Katsuki
Motoya
M
Kuroki
Toshio
T
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000201:enzymology; D051379:Mice; D011493:Protein Kinase C / Q000172:deficiency* / Q000502:physiology; D012867:Skin / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate; D014945:Wound Healing / Q000502:physiology*
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; C081975:protein kinase C eta; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate