title: TGF-beta and cancer.
abstract: The relationships between transforming growth factor-beta (TGF-beta) and cancer are varied and complex. The paradigm that is emerging from the experimental evidence accumulated over the past decade or so is that TGF-beta can play two different and opposite roles with respect to the process of malignant progression. During early stages of carcinogenesis, TGF-beta acts predominantly as a potent tumor suppressor and may mediate the actions of chemopreventive agents such as retinoids and nonsteroidal anti-estrogens. However, at some point during the development and progression of malignant neoplasms, bioactive TGF-betas make their appearance in the tumor microenvironment and the tumor cells escape from TGF-beta-dependent growth arrest. In many cases, this resistance to TGF-beta is the consequence of loss or mutational inactivation of the genes that encode signaling intermediates. These include the types I and II TGF-beta receptors, as well as receptor-associated and common-mediator Smads. The stage of tumor development or progression at which TGF-beta-resistant clones come to dominate the tumor cell population in different types of neoplasm remains to be defined. The phenotypic switch from TGF-beta-sensitivity to TGF-beta-resistance that occurs during carcinogenesis has several important implications for cancer prevention and treatment.
authors.affiliation: Department of Medicine (Medical Oncology) and Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, CT, USA.
authors.forename: M
authors.initials: M
authors.lastname: Reiss
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000276:immunology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
chemical_list: D015534:Trans-Activators; D016212:Transforming Growth Factor beta