Transforming growth factor-β and breast cancer: Cell cycle arrest by transforming growth factor-β 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)-β mediates G(1) 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-β are reviewed. Loss of growth inhibition by TGF-β 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 G(1) arrest by TGF-β. Elucidation of these pathways in breast cancer may ultimately lead to novel and more effective treatments for this disease.