Table 1 Growth factor receptor antagonists consistently activated FOXO3a in sensitive breast cancer cells

Hegde (2007) [22]

Lapatinib

Activates in responsive cell lines; measured as Thr³² P-FOXO3a and by microarray, BT474 and SKBr3. No effect in resistant cell lines; MDA-MB-468 and T47D.

Decreased expression of glyceraldehyde-3-phosphate dehydrogenase, enolase 1, pyruvate kinase and fatty acid synthase expression in BT474 and SKBr3

Growth rate reduced in BT474 and SKBr3

Karadedou (2012) [23]

Lapatinib

Activates in BT474 or SKBR3 measured by FOXO3a nuclear translocation.

Decreased expression of VEGF.

Real PJ (2005) [20]

Trastuzumab

Activates in MB231 and SUM159, primary breast effusions; measured as nuclear translocation of FOXO3a.

Up-regulation of Bnip1.

Increased sensitivity to apoptosis.

Krol (2007) [19]

Gefitinib

Activates in BT474 and SKBR3, but no effect in gefitinib-resistant lines MCF-7, MDA-MB-231, and MDA-MB-453. Measured as Thr³² P-FOXO3a and nuclear translocation analysis.

Cell cycle arrest predominantly at the G(0)-G(1) phase and apoptosis.

McGovern (2009) [21]

Gefitinib

Activates in BT474 and SKBR3 but not the gefitinib-resistant lines MCF-7, MDA-MB-231, and MDA-MB-453. Measured as nuclear FOXO3a and microarray.

Increase in Bim, p27 ^kip1