Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement.
A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8.
Basolo
Fulvio
F
Dipartimento di Oncologia, Università degli Studi di Pisa, Pisa, Italy. f.basolo@do.med.unipi.it
Giannini
Riccardo
R
Toniolo
Antonio
A
Casalone
Rosario
R
Nikiforova
Marina
M
Pacini
Furio
F
Elisei
Rossella
R
Miccoli
Paolo
P
Berti
Piero
P
Faviana
Pinuccia
P
Fiore
Lisa
L
Monaco
Carmen
C
Pierantoni
Giovanna Maria
GM
Fedele
Monica
M
Nikiforov
Yuri E
YE
Santoro
Massimo
M
Fusco
Alfredo
A
D000328:Adult; D000818:Animals; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D025741:HMGA1a Protein / Q000096:biosynthesis / Q000235:genetics; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis; D007621:Karyotyping; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; D015850:Interleukin-6; D016209:Interleukin-8; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; C499496:Pax8 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015534:Trans-Activators; D025741:HMGA1a Protein; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human