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

Chih Ming Chou, Yi Chung Chen, San Su, Gen Der Chen, Kai Yun Huang, Huang Wei Lien, Chang Jen Huang, Chia Hsiung Cheng

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number102
JournalJournal of Biomedical Science
Volume22
Issue number1
DOIs
Publication statusPublished - Nov 17 2015

Fingerprint

Papilloma
Zebrafish
Biomedical Research
Skin
Chemical activation
Fertilization
Tumors
Epidermis
MAP Kinase Kinase 1
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases
Cell proliferation
Mitogen-Activated Protein Kinases
Preclinical Drug Evaluations
Fish
COS Cells
Assays
Screening
Neoplasms
Fishes

Keywords

  • MEK2
  • Papilloma
  • Proliferation
  • Skin
  • Zebrafish

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Activation of MEK2 is sufficient to induce skin papilloma formation in transgenic zebrafish Application of Zebrafish in Biomedical Research. / Chou, Chih Ming; Chen, Yi Chung; Su, San; Chen, Gen Der; Huang, Kai Yun; Lien, Huang Wei; Huang, Chang Jen; Cheng, Chia Hsiung.

In: Journal of Biomedical Science, Vol. 22, No. 1, 102, 17.11.2015.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Chen, Gen Der

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AU - Lien, Huang Wei

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AU - Cheng, Chia Hsiung

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