Lack of responsiveness to TGF-β1 in a thyroid carcinoma cell line with functional type I and type II TGF-β receptors and Smad proteins, suggests a novel mechanism for TGF-β insensitivity in carcinoma cells

Differential Activation of Smads in HeLa and SiHa Cells That Differ in Their Response to Transforming Growth Factor-β

“…Even though a small fraction of the HeLa cells showed a nuclear accumulation of activated Smads, the effects exerted by TGF-␤ on cell cycle do not seem to depend on this activation of Smads as the inhibi- (34 -36). TGF-␤ insensitivity may also involve novel mechanisms independent of Smads (33,37).…”

BMP-7-Induced Cell Cycle Arrest of Anaplastic Thyroid Carcinoma Cells via p21CIP1 and p27KIP1

“…TGF-␤ is well known for its growth inhibitory action in a variety of cell types (18,19,22,29,42), including both normal (5) and malignant thyroid cells (6). The role of the closely related family of BMPs on cell growth is still largely unknown.…”

“…TGF-␤, activin, and bone morphogenetic protein (BMP), in the regulation of thyroid growth and function has become evident from numerous studies (3)(4)(5). Recently, we demonstrated an inhibitory effect of TGF-␤ on the proliferation of human anaplastic thyroid carcinoma cells in culture, showing a retained sensitivity of the highly malignant tumor cells to negative regulation of cell growth (6).…”

Cellular growth inhibition by TGF-$beta;1 involves IRS proteins*1

“…Accumulating evidence indicates that these two activities are uncoupled in many human carcinoma cells [5][6][7][8][9][10]. Such cells fail to respond to growth inhibition by TGF-b but exhibit TGF-b-mediated transcriptional activation of extracellular matrix synthesis-related genes; this is known to be primarily mediated by the type I/type II TGF-b receptor (TbR-I/TbR-II) heterocomplex in the cell systems studied so far [11,12].…”