title: Upregulation of the PI3K/Akt pathway in the tumorigenesis of canine thyroid carcinoma.
abstract: BACKGROUND
  Information on the genetic events leading to thyroid cancer in dogs is lacking.
  
  
  OBJECTIVE
  Upregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs.
  
  
  METHODS
  Fifty-nine dogs with thyroid carcinoma and 10 healthy controls.
  
  
  METHODS
  Quantitative RT-PCR was performed for VEGFR-1, VEGFR-2, EGFR, PIK3CA, PIK3CB, PDPK1, PTEN, AKT1, AKT2, COX-2, and CALCA. Mutation analysis was performed for known hotspots of RAS (N, K, H), PIK3CA, BRAF, RET, and for the entire coding region of PTEN.
  
  
  RESULTS
  Forty-three dogs (73%) had follicular cell thyroid carcinoma (FTC) and 16 dogs (27%) had medullary thyroid carcinoma (MTC). The relative mRNA expressions of VEGFR-1 (P < .001), VEGFR-2 (P = .002), PDPK1 (P < .001), AKT1 (P = .009), and AKT2 (P < .001) were increased in FTC, and those of EGFR (P < .001), VEGFR-1 (P = .036), and PIK3CA (P = .019) were increased in MTC when compared to normal thyroid glands. Mutation analysis of K-RAS identified 2 activating missense mutations, which also have been described in thyroid cancer of humans. A G12R substitution was present in 1 FTC and an E63K substitution was present in 1 MTC. No functional mutations were found in the sequenced regions of H-RAS, N-RAS, PIK3CA, BRAF, RET, and PTEN.
  
  
  CONCLUSIONS
  The increased expression of several genes associated with PI3K/Akt signaling suggests the involvement of this pathway in the pathogenesis of thyroid carcinoma in dogs, warranting further research on pathway activation and gene amplification. The mutations most frequently associated with thyroid cancer in humans are rare in dogs.
authors.affiliation: Department of Medicine and Clinical Biology of Small Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Campos
authors.forename: M M J
authors.initials: MM
authors.lastname: Kool
authors.forename: S
authors.initials: S
authors.lastname: Daminet
authors.forename: R
authors.initials: R
authors.lastname: Ducatelle
authors.forename: G
authors.initials: G
authors.lastname: Rutteman
authors.forename: H S
authors.initials: HS
authors.lastname: Kooistra
authors.forename: S
authors.initials: S
authors.lastname: Galac
authors.forename: J A
authors.initials: JA
authors.lastname: Mol
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary; D000818:Animals; D018278:Carcinoma, Neuroendocrine / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary; D016022:Case-Control Studies; D004283:Dog Diseases / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000662:veterinary; D015398:Signal Transduction / Q000502:physiology*; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000662:veterinary*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: C-cell; Dog; Follicular; Medullary; RAS