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 dysregulatio n are hallmarks of cancer. The cell cycle is governed by cyclin-dependent k inases (cdks) that integrate mitogenic and growth inhibitory signals. Trans forming growth factor (TGF)-beta mediates G(1) cell cycle arrest by inducin g or activating cdk inhibitors, and by inhibiting factors required for cdk activation. Mechanisms that lead to cell cycle arrest by TGF-beta are revie wed. Loss of growth inhibition by TGF-beta occurs early in breast cell tran sformation, 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-beta. Elucidation of these pathways in breast cancer may ultimately lead to novel and more effective treatments for this disease.