Related Experiment Video
Updated: May 10, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Comparative analysis of MAPK and PI3K/AKT pathway activation and inhibition in human and canine melanoma
J S Fowles1,2, C L Denton2, D L Gustafson1,2
1Cell and Molecular Biology Program, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
Abstract:
The lack of advanced animal models of human cancers is considered a barrier to developing effective therapeutics. Canine and human melanomas are histologically disparate but show similar disease progression and response to therapies. The purpose of these studies was to compare human and canine melanoma tumours and cell lines regarding MAPK and PI3K/AKT signalling dysregulation, and response to select molecularly targeted agents. Pathway activation was investigated via microarray and mutational analysis. Growth inhibition and cell cycle effects were assessed for pathway inhibitors AZD6244 (MAPK) and rapamycin (PI3K/AKT) in human and canine melanoma cells. Human and canine melanoma share similar differential gene expression patterns within the MAPK and PI3K/AKT pathways. Constitutive pathway activation and similar sensitivity to AZD6244 and rapamycin was observed in human and canine cells. These results show that human and canine melanoma share activation and sensitivity to inhibition of cancer-related signalling pathways despite differences in activating mutations.
Insights
Canine and human melanomas share similar signaling pathway activation and drug responses, offering a valuable comparative model for cancer therapy development. This research highlights shared therapeutic targets despite histological differences.
Area of Science:
- Comparative oncology
- Molecular biology
- Cancer therapeutics
Background:
- Advanced animal models are crucial for effective cancer therapeutics development.
- Canine and human melanomas, though histologically different, exhibit similar disease progression and therapeutic responses.
Purpose of the Study:
- To compare MAPK and PI3K/AKT signaling pathway dysregulation in human and canine melanoma.
- To assess the response of human and canine melanoma cells to targeted molecular agents.
Main Methods:
- Microarray and mutational analysis were used to investigate pathway activation.
- Growth inhibition and cell cycle effects were evaluated using MAPK inhibitor AZD6244 and PI3K/AKT inhibitor rapamycin.
Main Results:
- Human and canine melanomas displayed similar differential gene expression patterns in MAPK and PI3K/AKT pathways.
- Both human and canine melanoma cells showed constitutive pathway activation.
- Similar sensitivity to AZD6244 and rapamycin was observed in both species' melanoma cells.
Conclusions:
- Human and canine melanomas share common activation patterns in cancer-related signaling pathways.
- Despite histological differences, canine melanoma serves as a relevant model for studying human melanoma signaling and response to targeted therapies.
Related Concept Videos
MAPK Signaling Cascades
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...

