Molecular and Cell Biology of TGF-β

Abstract

The TGF-βs are a remarkable set of peptides consisting of three highly homologous isoforms, TGF-β 1, 2, and 3. Distinguished initially for their ability to inhibit the growth of most epithelial and hematopoietic cells and to regulate the production of extracellular matrix by mesenchymal cells, these peptides are now known to act via autocrine, paracrine, and endocrine modes to control a wide variety of developmental processes and to play key roles in the pathogenesis of many diseases including especially fibrotic diseases, parasitic diseases, autoimmune diseases, and carcinogenesis. The activity of these peptides is under tight control by processes including regulation of the expression of the isoforms and their receptors and of the trafficking and activation of their latent forms.

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

“…TGF-β1 is a member of a large family of growth and differentiation factors that are involved in cell division, differentiation, migration, adhesion, death, extracellular matrix production, tissue homeostasis and embryogenesis (20,28,33). It express constitutively in a wide variety of cell types.…”

A Novel Transforming Growth Factor-β Receptor-interacting Protein That Is Also a Light Chain of the Motor Protein Dynein

“…Transforming growth factor-␤ (TGF␤) is the prototype for the TGF␤ superfamily of highly conserved growth regulatory polypeptides that also includes the activins, inhibins, bone morphogenetic proteins, decapentaplegic (Dpp), nodal, Lefty, and others (Roberts, 1998;Sporn and Vilcek, 2000;Yue and Mulder, 2001). Alterations in the TGF␤ signaling components and pathways have been implicated in a vast array of human pathologies, including cancer (Massague et al, 2000;Sporn and Vilcek, 2000;Derynck et al, 2001).…”

“…TGF␤ binds to two types of transmembrane serine/threonine kinase receptors (RI and RII) in a heterotetrameric complex, to activate downstream components (Roberts, 1998; Massague et al, 2000;Sporn and Vilcek, 2000;Yue and Mulder, 2001). The Smad family of signaling intermediates plays an important role in mediating TGF␤ responses (Attisano and Wrana, 2000;ten Dijke et al, 2000;Yue and Mulder, 2001).…”

Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells

“…25 However, in vitro, total TGFb levels (active plus latent forms) can be measured by performing an in vitro acid activation step. 26 Under the current assay conditions, all cell lines tested, except 1542NPTX and 1532CP1TX, secreted signi®cantly higher amounts of TGFb1, as compared to normal prostate NPEC cells ( Figure 3A).…”

“…As in vitro response pro®les to TGFb subspecies 1 ± 3 tend to be similar across a variety of systems and as this was previously shown to be the case for growth inhibition of prostate, only growth inhibition in response to TGFb1 was measured in the current study. 17,25 The IC50s for growth inhibition by TGFb1 are depicted in Table 2. No pattern of sensitivity was evident, with relative resistance (ie IC50 b 0.5 ng/ml) being observed in two of three established cell lines and in three of ®ve non-established cell lines.…”