Transforming growth factor-beta and breast cancer: Cell cycle arrest by transforming growth factor-beta and its disruption in cancer.
Altered responsiveness to extracellular signals and cell cycle dysregulation are hallmarks of cancer. The cell cycle is governed by cyclin-dependent kinases (cdks) that integrate mitogenic and growth inhibitory signals. Transforming growth factor (TGF)-beta mediates G1 cell cycle arrest by inducing or activating cdk inhibitors, and by inhibiting factors required for cdk activation. Mechanisms that lead to cell cycle arrest by TGF-beta are reviewed. Loss of growth inhibition by TGF-beta occurs early in breast cell transformation, and may contribute to breast cancer progression. Dysregulation of cell cycle effectors at many different levels may contribute to loss of G1 arrest by TGF-beta. Elucidation of these pathways in breast cancer may ultimately lead to novel and more effective treatments for this disease.
Donovan
J
J
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M3N 3M5.
Slingerland
J
J
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D016213:Cyclins / Q000378:metabolism; D005260:Female; D016259:Genes, myc / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D010766:Phosphorylation; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016213:Cyclins; D016212:Transforming Growth Factor beta