Molecular and genotypic characterization of human thyroid follicular cell carcinoma-derived cell lines.
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Meireles
Ana Margarida
AM
Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto, Portugal.
Preto
Ana
A
Rocha
Ana Sofia
AS
Rebocho
Ana Paula
AP
Máximo
Valdemar
V
Pereira-Castro
Isabel
I
Moreira
Severina
S
Feijão
Tália
T
Botelho
Tiago
T
Marques
Ricardo
R
Trovisco
Vítor
V
Cirnes
Luís
L
Alves
Cíntia
C
Velho
Sérgia
S
Soares
Paula
P
Sobrinho-Simões
Manuel
M
D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology