Inhibition of heregulin mediated MCF-7 breast cancer cell growth by the ErbB3 binding protein EBP1.

The ErbB2/3 heterodimer plays a critical role in breast cancer genesis and progression. EBP1, an ErbB3 binding protein, inhibits breast cancer growth but its effects on ErbB3 ligand mediated signal transduction or ErbB receptors is not known. We report here that ectopic expression of EBP1 in MCF-7 and AU565 breast cancer cell lines inhibited HRG-induced proliferation.

Ebp1-mediated inhibition of cell growth requires serine 363 phosphorylation.

Ebp1 is an ErbB3 binding phosphoprotein with pleiotropic effects. Overexpression of Ebp1 represses transcription of E2F1 responsive cell cycle regulated genes and inhibits cell growth. However, the effect of phosphorylation on Ebp1-mediated transcriptional repression and cell growth inhibition is currently unknown.

The ErbB3 binding protein Ebp1 interacts with Sin3A to repress E2F1 and AR-mediated transcription.

Ectopic expression of ebp1, a member of the PA2G4 family, inhibits the proliferation and induces the differentiation of human breast and prostate cancer cell lines. Ebp1 inhibits transcription of E2F1 and androgen receptor regulated genes such as prostate specific antigen (PSA) through its interactions with histone deacetylases (HDACs). To further understand Ebp1's interactions with other components of the transcriptional repression machinery, we examined the association of Ebp1 with the corepressor Sin3A.

The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells.

Down-regulation of the androgen receptor (AR) is being evaluated as an effective therapy for the advanced stages of prostate cancer. We report that Ebp1, a protein identified by its interactions with the ErbB3 receptor, down-regulates expression of AR and AR-regulated genes in the LNCaP prostate cancer cell line. Using microarray analysis, we identified six endogenous AR target genes, including the AR itself, that are down-regulated by ebp1 overexpression.

The N-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest.

Although phosphoinositide 3-kinase (PI 3-kinase) is essential for cell cycle progression, the molecular mechanisms that regulate its diverse biological effects are poorly understood. We demonstrate here that Rb, a key regulator of cell cycle progression, associates with p55 kDa (p55alpha and p55gamma) regulatory subunits of PI 3-kinase in vivo and in vitro. Both confocal microscopy and biochemical analysis demonstrated the presence of p55gamma in the nucleus.