Transforming growth factor-beta and breast cancer: Transforming growth factor-beta/SMAD signaling defects and cancer.
Transforming growth factor-beta (TGF-beta) is a tumor suppressor, the function of which is compromised in many types of human cancer, including breast cancer. The tumor suppressive effects of TGF-beta are caused by potent inhibition of cell proliferation due to cell cycle arrest in the G1 phase. Such antiproliferative responses are mediated by a signaling system that includes two types of cell surface receptors and intracellular signal transducers, the SMAD proteins. Different molecular mechanisms can lead to loss of antiproliferative TGF-beta responses in tumor cells, including mutations in components of the signaling system and inhibition of the SMAD signaling pathway by aberrant activities of various regulatory molecules. Some of these mechanisms will be discussed, with emphasis on their potential involvement in breast tumorigenesis.
Kretzschmar
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Ruttenberg Cancer Center, NYU-Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. kretzm01@doc.mssm.edu
D001943:Breast Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases