It has been demonstrated that transforming growth factor-beta (TGF beta) and other members of TGF beta 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 TGF beta 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 TGF beta signaling and for some of the TGF beta-mediated biological effects. The overexpression of SMAD4, restoring TGF beta transduction, determined a significant increase of antiproliferative response to TGF beta, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis. Journal of Molecular Endocrinology (2010) 45, 229-244
Role of reduced expression of SMAD4 in papillary thyroid carcinoma / D'Inzeo, Sonia; Nicolussi, Arianna; A., Ricci; Mancini, Patrizia; A., Porcellini; Nardi, Francesco; Coppa, Anna. - In: JOURNAL OF MOLECULAR ENDOCRINOLOGY. - ISSN 0952-5041. - STAMPA. - 45:4(2010), pp. 229-244. [10.1677/jme-10-0044]
Role of reduced expression of SMAD4 in papillary thyroid carcinoma
D'INZEO, SONIA;NICOLUSSI, Arianna;MANCINI, Patrizia;NARDI, Francesco;COPPA, Anna
2010
Abstract
It has been demonstrated that transforming growth factor-beta (TGF beta) and other members of TGF beta 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 TGF beta 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 TGF beta signaling and for some of the TGF beta-mediated biological effects. The overexpression of SMAD4, restoring TGF beta transduction, determined a significant increase of antiproliferative response to TGF beta, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis. Journal of Molecular Endocrinology (2010) 45, 229-244I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
