CSrc and Her2 Signaling Pathways Cooperate With Estrogen to Promote Estrogen Receptor Phosphorylation, Ubiquitination and Proteolysis in ER Negative Breast Cancers
Abstract
Oncogenic activation of ErbB2 and cSrc signaling pathways have been associated with worst prognosis and a more aggressive breast cancer phenotype. Here we explored the role of cSrc and ErbB2 as potentially contributing to estrogen receptor (ER) loss in ER protein negative (ER-) breast cancers. Our studies indicate that Src or proteasome inhibition increased ER levels in MCF-7, MDA- MB-361 and BT20. Furthermore, we have shown that Src activation cooperates with ligand to stimulate ER proteolysis and transcriptional activity. GW572016, an ErbB1 and ErbB2 inhibitor, decreased ER transcriptional activity in MCF-7 cells. ER- primary breast cancers and cell lines showed increased Src activity compared to ER+ cancers and cell lines, and the ER protein t1/2 was reduced in ER- breast cancer lines. Thus, these data provide a novel link between Src activation and the ER- tumor status and support a model whereby Src may promote transcription coupled ER proteolysis in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA435298
Entities
People
- Isabel Chu
Organizations
- University of Miami