Transforming growth factor beta regulation of cell proliferation.
Two types of transforming growth factors (TGF) have been purified and well characterized, TGF alpha and TGF beta. TGF alpha is a 5.6 kD single chain molecule that shows sequence homology to epidermal growth factor (EGF), binds to the EGF receptor, and has biological effects very similar to those of EGF. TGF beta is different from TGF alpha in its molecular structure and biological activity, and has its own specific cell surface receptor. TGF beta is a 25 kD homodimer of 12.5 kD subunits that shows no sequence homology to TGF alpha. TGF beta is a highly ubiquitous molecule produced by a variety of cell types in an inactive form. Most cells have receptors for TGF beta, suggesting that a major regulatory step in TGF beta action is through activation of the inactive form. Growth stimulatory effects with TGF beta have been observed so far only in fibroblastic cells. In at least one circumstance, there is evidence that the stimulatory effects of TGF beta in fibroblastic cells is indirect through induction of c-sis and autocrine stimulation by platelet-derived growth factor (PDGF)-like material. TGF beta inhibits in vitro proliferation of most cell types tested, including normal epithelial cells. Thus TGF beta is primarily a growth inhibitor and not a classical growth factor. Increased autocrine stimulation by endogenous TGF beta in fibroblastic cells or decreased inhibitory effects in epithelial cells (or other cells normally inhibited by TGF beta) could lead to an increased proliferative potential and thereby contribute to the neoplastic phenotype.
Moses
H L
HL
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37322.
Coffey
R J
RJ
Leof
E B
EB
Lyons
R M
RM
Keski-Oja
J
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006133:Growth Substances / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D009626:Terminology as Topic; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D010455:Peptides; D015291:Transforming Growth Factors