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Molecular study of signaling-pathway genes in experimental rat thyroid carcinoma.

AbstractINTRODUCTION:
A study was conducted on histological patterns and biomolecular changes in Goitrogen-induced experimental rat thyroid tumors. The link between the histological types observed and N-ras, B-raf, and PI3KCA gene mutations widely reported in human thyroid cancers was explored.
MATERIAL AND METHODS:
An analysis was done on paraffin-embedded tumor tissue sections from Wistar rats receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking-water supply over an 18-month period. Three experimental subgroups were formed, each comprising 10 thyroids: subgroup I (control) consisted of thyroids from untreated controls; subgroups II and III (experimental) consisted of thyroids from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no metastasis (II), or distant metastasis (III). DNA was extracted from paraffin-embedded tissues. To test for the genetic mutations most widely reported in human thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and exon 15 of the B-raf gene were amplified and sequenced.
RESULTS:
All tumors were of the follicular type. None of the 20 experimental rat thyroids displayed the expected gene mutations reported in humans. However, 90% of them contained four new B-raf gene mutations and all were silent and did not cause an amino acid substitution in the protein chain.
CONCLUSIONS:
Biomolecular analysis suggested that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor formation using the experimental procedure applied in this study. But the four mutations in B-raf, though without functional repercussions, may be a specific marker for this tumor type.
AuthorsMaría Inés Carmona-López, Manuel De Miguel, Hugo Galera-Ruiz, María José Ríos-Moreno, Ana Fernández, Hugo Galera-Davidson
JournalEndocrine research (Endocr Res) Vol. 37 Issue 4 Pg. 188-96 ( 2012) ISSN: 1532-4206 [Electronic] England
PMID22630346 (Publication Type: Journal Article)
Chemical References
  • Perchlorates
  • Potassium Compounds
  • potassium perchlorate
  • Braf protein, rat
  • Proto-Oncogene Proteins B-raf
Topics
  • Adenocarcinoma, Follicular (chemically induced, genetics, pathology)
  • Animals
  • Base Sequence
  • Exons
  • Female
  • Genes, ras
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Perchlorates (toxicity)
  • Potassium Compounds (toxicity)
  • Proto-Oncogene Proteins B-raf (genetics)
  • Rats
  • Rats, Wistar
  • Sequence Analysis, DNA
  • Signal Transduction (drug effects, genetics)
  • Thyroid Neoplasms (chemically induced, genetics, pathology)

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