Role of reduced expression of SMAD4 in papillary thyroid carcinoma.

It has been demonstrated that transforming growth factor-b (TGFb) and other members of TGFb 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 TGFb 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 TGFb signaling and for some of the TGFb-mediated biological effects. The overexpression of SMAD4, restoring TGFb transduction, determined a significant increase of antiproliferative response to TGFb, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis.