Activation of MEK2 is sufficient to induce skin papilloma formation in transgenic zebrafish
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Updated: Mar 30, 2026
Live Imaging of Innate Immune and Preneoplastic Cell Interactions Using an Inducible Gal4/UAS Expression System in Larval Zebrafish Skin
Published on: February 3, 2015
Chih-Ming Chou1,2, Yi-Chung Chen3, San Su4
1Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 110, Taiwan. cmchou@tmu.edu.tw.
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.
Insights
Mitogen-activated protein kinase kinase 2 (MEK2) can cause skin tumors by activating MAPK signaling. A new zebrafish model shows MEK2
Area of Science:
- Oncology
- Molecular Biology
- Zebrafish Models
Background:
- Mutations in MEK1 are linked to cell proliferation and tumor formation.
- The specific role of MEK2 in these processes is less understood.
- A novel transgenic zebrafish model, Tg(krt14:MEK2S219D-GFP), was created to investigate MEK2's function in skin tumorigenesis.
Purpose of the Study:
- To elucidate the role of MEK2 in skin tumor formation using a zebrafish model.
- To investigate the signaling pathways involved in MEK2-induced skin papillomas.
Main Methods:
- Establishment of a constitutive MEK2 transgenic zebrafish line (Tg(krt14:MEK2S219D-GFP)).
- Analysis of extracellular signal-regulated kinase 1 (ERK1) phosphorylation.
- Induction of epidermal papillary formation and skin papillomas.
- Immunohistochemical detection of phospho-ERK.
- Inhibition of MEK signaling using U0126.
- In vitro and in vivo cell proliferation assays (Ki-67 staining).
Main Results:
- Constitutive MEK2 and MEK1 phosphorylate ERK1.
- Transient expression of MEK2 or MEK1 induced epidermal papillary formation.
- Tg(krt14:MEK2S219D-GFP) zebrafish developed skin papillomas within 6 days post-fertilization.
- Phospho-ERK signals were detected in papilloma sections.
- MEK inhibition (U0126) significantly reduced papilloma formation.
- Increased cell proliferation was observed in vitro and in vivo.
Conclusions:
- MEK2 is sufficient to induce epidermal papilloma formation via MAPK signaling in zebrafish.
- The Tg(krt14:MEK2S219D-GFP) zebrafish model provides a new platform for anti-cancer drug screening.
