Activation of MEK2 is sufficient to induce skin papilloma formation in transgenic zebrafish Application of Zebrafish in Biomedical Research

Background: mutations in mitogen-activated protein kinase (mapk) kinase 1 (mek1) that occur during cell proliferation and tumor formation are well described. information on the roles of mek2 in these effects is still limited. we established a constitutive mek2 transgenic zebrafish,tg(krt14:mek2s219d-gfp),to elucidate the role of mek2 in skin tumor formation. results: we found that both constitutive mek2 and mek1 are able to phosphorylate the extracellular signal-regulated kinase 1 (erk1) protein. transient expression of constitutive mek2 and mek1 in the zebrafish epidermis induced papillary formation at 48 h post-fertilization,but no effects were observed due to the expression of mek1,mek2,or the dominant negative form of mek2. the transgenic zebrafish,tg(krt14:mek2s219d-gfp),developed skin papillomas in the epidermis within 6 days post-fertilization (dpf). the phospho-erk signal was detected in section of skin papillomas in an immunohistochemical experiment. treatment with 50 μm of the mek inhibitor,u0126,had significantly decreased the skin papilloma formation in tg(krt14:mek2s219d-gfp) zebrafish by 6 dpf. in vitro and in vivo proliferation assay in cos-1 cells and in tg(krt14:mek2s219d-gfp) transgenic fish show significantly increased cell number and ki-67 signaling. conclusion: our data indicate that mek2 is sufficient to induce epidermal papilloma formation through mapk signaling in zebrafish,and this transgenic model can be used as a new platform for drug screening. © 2015 chou et al.