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- Title
Autocrine stimulation by osteopontin plays a pivotal role in the expression of the mitogenic and invasive phenotype of RET/PTC-transformed thyroid cells.
- Authors
Castellone, Maria Domenica; Celetti, Angela; Guarino, Valentina; Cirafici, Anna Maria; Basolo, Fulvio; Giannini, Riccardo; Medico, Enzo; Kruhoffer, Mogens; Curcio, Francesco; Fusco, Alfredo; Melillo, Rosa Marina; Orntoft, Torben F.; Santoro, Massimo
- Abstract
Papillary thyroid carcinomas are characterized by rearrangements of the RET receptor tyrosine kinase generating RET/PTC oncogenes. Here we show that osteopontin (OPN), a secreted glycoprotein, is a major RET/PTC-induced transcriptional target in PC Cl 3 thyroid follicular cells. OPN upregulation depended on the integrity of the RET/PTC kinase and tyrosines Y1015 and Y1062, two major RET/PTC autophosphorylation sites. RET/PTC also induced a strong overexpression of CD44, a cell surface signalling receptor for OPN. Upregulation of CD44 was dependent on RET/PTC Y1062, as well. Constitutive OPN overexpression or treatment with exogenous recombinant OPN sharply increased proliferation, Matrigel invasion and spreading in collagen gels of RET/PTC-transformed PC Cl 3 cells. These effects were impaired by the treatment of PC Cl 3-RET/PTC cells with OPN- and CD44-locking antibodies. Thus, RET/PTC signalling triggers an autocrine loop involving OPN and CD44 that sustains proliferation and invasion of transfomed PC Cl 3 thyrocytes.Oncogene (2004) 23, 2188-2196. doi:10.1038/sj.onc.1207322 Published online 23 February 2004
- Subjects
THYROID cancer; OSTEOPONTIN; ONCOGENES; PROTEIN-tyrosine kinases; GENETIC transcription
- Publication
Oncogene, 2004, Vol 23, Issue 12, p2188
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207322