Peer-reviewed veterinary case report
SET protein blockers as a treatment for melanoma in dogs
By Enjoji, Shuhei et al.·Published in The Journal of veterinary medical science·2015·Joint Faculty of Veterinary Medicine, Japan·View original on PubMed →
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Original publication title: The therapeutic effects of SET/I2PP2A inhibitors on canine melanoma.
- Species:
- dog
Plain-English summary
A study looked at how certain treatments could help dogs with melanoma, a serious skin cancer. Researchers found that using SET inhibitors, like OP449 and FTY720, was effective in killing cancer cells from metastatic melanoma (cancer that has spread) more than from primary melanoma. The treatments worked by activating a tumor-suppressing protein, which slowed down the growth and spread of the cancer cells. This suggests that SET inhibitors could be a promising option for treating dogs with advanced melanoma.
People also search for: dog melanoma treatment · canine skin cancer therapy · SET inhibitors for dogs
Abstract
Canine melanoma is one of the most important diseases in small animal medicine. Protein phosphatase 2A (PP2A), a well conserved serine/threonine phosphatase, plays a critical role as a tumor suppressor. SET/I2PP2A is an endogenous inhibitor for PP2A, which directly binds to PP2A and suppresses its phosphatase activity. Elevated SET protein levels have been reported to exacerbate human tumor progression. The role of SET in canine melanoma, however, has not been understood. Here, we investigated the potential therapeutic role for SET inhibitors in canine melanoma. The expression of SET protein was observed in 6 canine melanoma cell lines. We used CMeC-1 cells (primary origin) and CMeC-2 cells (metastatic origin) to generate cell lines stably expressing SET-targeting shRNAs. Knockdown of SET expression in CMeC-2, but not in CMeC-1, leads to decreased cell proliferation, invasion and colony formation. Phosphorylation level of p70 S6 kinase was decreased by SET knockdown in CMeC-2, suggesting the involvement of mTOR (mammalian target of rapamycin)/p70 S6 kinase signaling. The SET inhibitors, OP449 and FTY720, more effectively killed CMeC-2 than CMeC-1. We observed PP2A activation in CMeC-2 treated with OP449 and FTY720. These results demonstrated the potential therapeutic application of SET inhibitors for canine melanoma.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/26062569/