Nucleophosmin is overexpressed in thyroid tumors.
Nucleophosmin (NPM) is a protein that contributes to several cell functions. Depending on the context, it can act as an oncogene or tumor suppressor. No data are available on NPM expression in thyroid cells. In this work, we analyzed both NPM mRNA and protein levels in a series of human thyroid tumor tissues and cell lines. By using immunohistochemistry, NPM overexpression was detected in papillary, follicular, undifferentiated thyroid cancer, and also in follicular benign adenomas, indicating it as an early event during thyroid tumorigenesis. In contrast, various levels of NPM mRNA levels as detected by quantitative RT-PCR were observed in tumor tissues, suggesting a dissociation between protein and transcript expression. The same behavior was observed in the normal thyroid FRTL5 cell lines. In these cells, a positive correlation between NPM protein levels, but not mRNA, and proliferation state was detected. By using thyroid tumor cell lines, we demonstrated that such a post-mRNA regulation may depend on NPM binding to p-Akt, whose levels were found to be increased in the tumor cells, in parallel with reduction of PTEN. In conclusion, our present data demonstrate for the first time that nucleophosmin is overexpressed in thyroid tumors, as an early event of thyroid tumorigenesis. It seems as a result of a dysregulation occurring at protein and not transcriptional level related to an increase of p-Akt levels of transformed thyrocytes.
Pianta
Annalisa
A
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy.
Puppin
Cinzia
C
Franzoni
Alessandra
A
Fabbro
Dora
D
Di Loreto
Carla
C
Bulotta
Stefania
S
Deganuto
Marta
M
Paron
Igor
I
Tell
Gianluca
G
Puxeddu
Efisio
E
Filetti
Sebastiano
S
Russo
Diego
D
Damante
Giuseppe
G
D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D000090243:Nucleophosmin; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D051057:Proto-Oncogene Proteins c-akt