Campos, Miguel; Kool, M M J; Daminet, S; Ducatelle, R; Rutteman, G; Kooistra, H S; Galac, S; Mol, J A (2014). Upregulation of the PI3K/Akt pathway in the tumorigenesis of canine thyroid carcinoma. Journal of veterinary internal medicine, 28(6), pp. 1814-1823. Wiley-Blackwell 10.1111/jvim.12435
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BACKGROUND
Information on the genetic events leading to thyroid cancer in dogs is lacking.
HYPOTHESIS/OBJECTIVES
Upregulation of the PI3K/Akt pathway has an important role in the tumorigenesis of thyroid carcinoma in dogs.
ANIMALS
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 AND CLINICAL IMPORTANCE
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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) |
UniBE Contributor: |
Campos, Miguel |
Subjects: |
600 Technology > 630 Agriculture |
ISSN: |
0891-6640 |
Publisher: |
Wiley-Blackwell |
Language: |
English |
Submitter: |
Miguel Fonseca e Campos |
Date Deposited: |
23 Sep 2016 12:52 |
Last Modified: |
05 Dec 2022 14:58 |
Publisher DOI: |
10.1111/jvim.12435 |
PubMed ID: |
25231196 |
Uncontrolled Keywords: |
C-cell; Dog; Follicular; Medullary; RAS |
BORIS DOI: |
10.7892/boris.88129 |
URI: |
https://boris.unibe.ch/id/eprint/88129 |
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