title: Identification of c-kit mutations-independent neoplastic cell proliferation of canine mast cells.
abstract: Gain-of-function mutations in the proto-oncogene c-kit have been considered the molecular mechanism of neoplastic proliferation of mast cells. However, the importance of c-kit gene mutations is not well evaluated in canine mast cell tumors (MCTs). In the present study, we established and characterized a mast cell line, HRMC, derived from a dog with MCT. We also examined c-kit mutations in HRMC cells and assessed an inhibitory effect of a tyrosine kinase inhibitor, STI571, on HRMC cells. HRMC cells had cytoplasmic metachromatic granules, chymase and tryptase, and expressed both KIT and FcepsilonRI on the cell surface. HRMC cells contained histamine and released beta-hexosaminidase through FcepsilonRI cross-linking and calcium ionophore stimulation. Nucleotide sequence analysis demonstrated no mutations in an open reading frame of c-kit cDNA and genomic DNA of the juxtamembrane domain of c-kit in HRMC cells. STI571 did not show any inhibitory effects on the proliferation of HRMC cells. These findings clearly demonstrated the existence of c-kit mutations-independent neoplastic canine mast cell proliferation. The growth factor-independent mast cell line established in this study might be valuable to explore novel mechanisms of c-kit mutations-independent neoplastic proliferation of mast cells in dogs.
authors.affiliation: Department of Veterinary Internal Medicine, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan. k-ohmori@cc.tuat.ac.jp
authors.forename: Keitaro
authors.initials: K
authors.lastname: Ohmori
authors.forename: Shinpei
authors.initials: S
authors.lastname: Kawarai
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Yasuda
authors.forename: Akane
authors.initials: A
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nishimura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sasaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Kenichi
authors.initials: K
authors.lastname: Masuda
mesh_terms: D000818:Animals; D001483:Base Sequence; D001549:Benzamides; D002460:Cell Line; D049109:Cell Proliferation; D004283:Dog Diseases / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D000068877:Imatinib Mesylate; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D034801:Mastocytoma / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit