Transforming Growth Factor β Receptors and p27kip in Thyroid Carcinoma

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Abstract
IN RECENT YEARS, a large body of evidence has accumulated with regard to the central role played by cell cycle regulatory mechanisms in many cancer types.1 The G1 phase of the cell cycle has proved to be a rate-limiting step beyond which cells are committed to division.2 Progression through this G1 checkpoint depends on the availability of specific growth factors and can be blocked by negative regulators such as transforming growth factor β (TGFβ). Current evidence indicates that the TGFβ receptors type I (TβR-I) and type II (TβR-II) are directly involved in TGFβ-mediated signal transduction. Signaling requires the formation of a heterotetramer containing 2 molecules each of TβR-I and TβR-II. A model for the mechanism of action of this complex has been proposed by Wrana and Attisano.3 According to this model, TβR-II is constitutively autophosphorylated, and ligand binding results in recruitment and phosphorylation of TβR-I. Kinase activity of TβR-I would then be responsible for the phosphorylation of unknown downstream substrates and the generation of biological responses.