Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.
Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.
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发表时间：
2003-05
期刊：
影响因子：
11.2
通讯作者：
K. Chida;T. Hara;Takaaki Hirai;C. Konishi;Kenji Nakamura;K. Nakao;A. Aiba;M. Katsuki;T. Kuroki
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作者：
K. Chida;T. Hara;Takaaki Hirai;C. Konishi;Kenji Nakamura;K. Nakao;A. Aiba;M. Katsuki;T. Kuroki
我们已经产生了一个小鼠品系缺乏蛋白激酶C（PKC）eta，以评估其在上皮组织和肿瘤形成的意义。PKCeta缺陷小鼠在两阶段皮肤癌发生中表现出对肿瘤形成的易感性增加，通过单次应用7，12-二甲基苯并（a）蒽（DMBA）用于肿瘤引发和重复应用12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）用于肿瘤促进。单独的DMBA或TPA处理没有增强肿瘤形成，表明PKCeta抑制肿瘤促进。在突变小鼠中，局部TPA治疗诱导的表皮增生延长。增强的肿瘤形成可能与局部TPA治疗诱导的延长的增生密切相关。在突变小鼠中，在通过打孔活检造成损伤后，背部皮肤上的伤口愈合，特别是上皮再生，显着延迟和结构受损。创伤愈合中上皮再生受损表明PKCeta在维持上皮结构中起作用的可能性。由PKCeta介导的上皮组织中的稳态对于体内肿瘤形成是重要的。我们认为PKCeta参与了体内上皮细胞增殖和重塑的调节，从而参与了肿瘤的形成。
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.