P44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis.
P44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis.
复制标题
DOI：
10.1158/0008-5472.can-05-3129
复制
发表时间：
2006-03-01
期刊：
影响因子：
11.2
通讯作者：
Pagès, G
中科院分区：
文献类型：
--
作者：
Bourcier, C;Jacquel, A;Pagès, G
细胞外信号调节激酶（ERK）响应于多种外部信号而调节细胞功能。然而，个别ERK亚型的具体功能在很大程度上是未知的。因此，我们研究了ERK 1基因敲除小鼠皮肤稳态和肿瘤发生中ERK 1的特异性功能。他们自发发展皮肤病变和角化过度与表皮厚度。在突变小鼠中，通过应用12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）诱导的皮肤过度增殖和炎症显著减少。ERKI-/-小鼠对由7，12-二甲基苯并（a）蒽（DMBA）诱导并由TPA促进的皮肤乳头状瘤的发展具有抗性。肿瘤出现延迟，它们的形成不那么频繁，它们的数量和大小减少。从基因敲除小鼠获得的角质形成细胞表现出生长减少和对凋亡信号的抵抗，伴随着与生长控制和侵袭性有关的基因表达受损。这些结果突出了ERK 1在皮肤稳态和皮肤肿瘤发展过程中的重要性。
Extracellular signal-regulated kinases (ERK) regulate cellular functions in response to a variety of external signals. However, the specific functions of individual ERK isoforms are largely unknown. Hence, we have investigated the specific function of ERK1 in skin homeostasis and tumorigenesis in ERK1 knockout mice. They spontaneously develop cutaneous lesions and hyperkeratosis with epidermis thickness. Skin hyperproliferation and inflammation induced by application of 12-O-tetradecanoylphorbol-13-acetate (TPA) is strongly reduced in mutant mice. ERKI-/- mice are resistant to development of skin papillomas induced by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by TPA. Tumor appearance was delayed, their formation was less frequent, and their number and size were reduced. Keratinocytes obtained from knockout mice showed reduced growth and resistance to apoptotic signals, accompanied by an impaired expression of genes implicated in growth control and invasiveness. These results highlight the importance of ERK1 in skin homeostasis and in the process of skin tumor development.