MKK4基因的抑癌及致癌作用

The Cancer Inhibition and Carcinogenicity of MKK4 Gene

丝裂原活化蛋白激酶激酶4(MKK4)基因为新近发现的肿瘤转移抑制基因。其编码蛋白可激活c-Jun氨基端激酶和p38这两条丝裂原活化蛋白激酶通路,将细胞外刺激信号转导至细胞核内,引起细胞的增殖、分化、转化及凋亡。MKK4基因具有抑癌作用,随着MKK4基因启动子区Rs3826392(T/G)位点G变异个数增加,结肠癌、肺癌及鼻咽癌的患病率会随之降低。与之相反,MKK4基因同时具有致癌作用,其表达上调可能与胰腺癌、前列腺癌的发生及浸润转移有关。

The mitogen-activated protein kinase 4 （MKK4） gene is recently recognized as a novel metastasis suppressor gene. Its protein could activate both of c-Jun N-terminal kinase （JNK） and p38 mitogenactivated protein kinase induced mitogen-activated protein kinase （MAPK） cascade to transduce extracellular signal into nucleus, and induee eeU proliferation, differentiation, transformation and apoptosis. The MKK4 gene could inhibit cancer initiation. Several studies had showed the initiation of colon ,lung and nasopharynx eancer was reduced along with the number increase of G mutation on the MKK4 promoter region Rs3826392 （T/G） site. On the contrary,MKK4 may also have careinogenicity. Various studies suggested the up-regulating of MKK4 might be related to the initiation, invasion and metastasis of pancreatic cancer and prostate