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Figure 2 | Breast Cancer Research

Figure 2

From: Transforming growth factor-β and breast cancer: Cell cycle arrest by transforming growth factor-β and its disruption in cancer

Figure 2

Mechanisms of cell cycle arrest by transforming growth factor (TGF)-β and their deregulation in cancer. TGF-β receptor activation leads to Smad2 phosphorylation. Phosphorylated Smad2 then binds Smad4 and the Smad2-Smad4 complex translocates to the nucleus to modulate transcription. Although p15 and p21 genes are induced and c-myc and Cdc25A repressed by TGF-β, these may not be direct effects of Smad2-Smad4 action (dotted lines). TGF-β inhibits G1 cyclin-cyclin-dependent kinases (cdks) by increasing p15 binding to cdk4 and cdk6 and by increasing p27 (+/-p21) binding to cyclin E-cdk2, thereby inhibiting retinoblastoma protein (pRb) phosphorylation. *Components of the TGF-β effector pathway that are mutated and/or functionally inactivated in human cancers; **molecules whose activation or overexpression may contribute to TGF-β arrest resistance.

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