Transforming growth factor-beta and suppression of carcinogenesis.
Transforming growth factor-beta (TGF-beta) plays an important role in controlling proliferation or differentiation in almost all epithelial tissues. The pathophysiology of TGF-beta during carcinogenesis is now an important area of investigation, since it appears that as the process of carcinogenesis progresses, epithelial cells often become refractory to the growth-regulatory actions of TGF-beta. In this article we consider the possible cellular and molecular bases for this phenomenon, and then discuss some pharmacological approaches to enhancing the synthesis or activity of TGF-beta. These approaches may provide new modalities for prevention of carcinogenesis, if they can be applied during the early stages of the disease process, before cells become refractory. We give particular attention to tamoxifen and retinoic acid, since it has been shown that these agents, which are of known efficacy for prevention of cancer, can markedly enhance the secretion of specific isotypes of TGF-beta by several types of cells.
Sporn
M B
MB
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892.
Roberts
A B
AB
Wakefield
L M
LM
Glick
A B
AB
Danielpour
D
D
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D051381:Rats; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013629:Tamoxifen / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D006131:Growth Inhibitors; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D014212:Tretinoin