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Molecular and genotypic characterization of human thyroid follicular cell carcinoma-derived cell lines.
Authors:Ana Margarida Meireles  Ana Preto  Ana Sofia Rocha  Ana Paula Rebocho  Valdemar Máximo  Isabel Pereira-Castro  Severina Moreira  Tália Feij?o  Tiago Botelho  Ricardo Marques  Vítor Trovisco  Luís Cirnes  Cíntia Alves  Sérgia Velho  Paula Soares  Manuel Sobrinho-Sim?es
Affiliation:Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal.
Abstract:
OBJECTIVE: Our aim was to characterize the molecular and genotypic profile of eight thyroid carcinoma-derived cell lines-TPC1, FB2, B-CPAP, K1, XTC-1, C643, 8505C, and Hth74-in order to use them as in vitro models of thyroid carcinogenesis. DESIGN: We evaluated the expression of five thyroid-specific genes (Tg, TSHr, TPO, PAX8, and TTF-1) to establish the cell lineage and to assess the differentiation status of each of the cell lines. We screened for mutations in the most relevant oncogenes/tumor suppressor genes affected in thyroid carcinogenesis: RAS, BRAF, CTNNB1, and TP53 along with RET/PTC rearrangements. Considering the putative relevance in general carcinogenesis, we have also studied other molecules such as EGFR, PI3K, RAF-1, and THRB. To determine the genetic identity of the cell lines, we performed genotypic analysis. MAIN OUTCOME: The panel of cell lines we have studied displayed activation of several oncogenes (BRAF, RAS, RET/PTC) and inactivation of tumor suppressor genes (TP53) known to be important for thyroid carcinogenesis. Two of the cell lines-TPC1 and FB2-shared the same genotypic profile, probably representing clones of an ancestor cell line (TPC1). CONCLUSION: Due to their different molecular alterations, these cell lines represent a valuable tool to study the molecular mechanisms underlying thyroid carcinogenesis. We suggest that genotypic analyses should be included as a routine procedure to guarantee the uniqueness of each cell line used in research.
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