Role of reduced expression of SMAD4 in papillary thyroid carcinoma.
It has been demonstrated that transforming growth factor-β (TGFβ) and other members of TGFβ superfamily play an important role in thyroid proliferative diseases. The deficiencies of SMAD4 are responsible to accelerate the malignant progression of neoplastic lesions in several types of tumors. Therefore, the objective of the present study was to determine the functional role of reduced expression of SMAD4 in human papillary thyroid carcinogenesis. For this purpose, we examined the TGFβ response in two cell lines, TPC-1 and BCPAP. Our data demonstrated for the first time that these cells showed a strong reduction in the level of SMAD4 protein, which was responsible for an alteration of TGFβ signaling and for some of the TGFβ-mediated biological effects. The overexpression of SMAD4, restoring TGFβ transduction, determined a significant increase of antiproliferative response to TGFβ, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis.
D'Inzeo
Sonia
S
Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, Rome, Italy.
Nicolussi
Arianna
A
Ricci
Antonella
A
Mancini
Patrizia
P
Porcellini
Antonio
A
Nardi
Francesco
F
Coppa
Anna
A
D002277:Carcinoma; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D021381:Protein Transport; D015398:Signal Transduction; D051901:Smad4 Protein / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
C497796:SMAD4 protein, human; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta