Hormonal Resistance and Metastasis: ER-coregulator-Src Signaling Targeted Therapy
Abstract
The estrogen receptor (ER), is implicated in the progression of breast cancer. Endocrine therapy is shown to have a positive effect on the treatment of breast cancer; however, initial or acquired resistance to endocrine therapies frequently occurs. In this study, we have generated model cells that have defects in either ER coregulator PELP1 or Src signaling axis. Using these models, we demonstrated that PELP1-Src axis play a key role in ER- extranuclear actions. Our data suggest that PELP1 and Src kinase axis also play an essential role in enhancing cell migration and metastasis. Pharmacological inhibition of Src kinase using dasatinib or Src knock down by shRNA significantly inhibited E2-mediated extranuclear actions in therapy resistant cells. The results from our study showed that ER-Src axis play an important role in promoting hormonal resistance by protooncogenes such as HER2, PELP1 and blocking this axis prevents the development of hormonal independence. Since PELP1 and Src kinase are commonly deregulated in breast cancers, combination therapies using both endocrine agents and dasatinib may have better therapeutic effect by delaying the development of hormonal resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2010
- Accession Number
- ADA535546
Entities
People
- Ratna K Vadlamudi
Organizations
- University of Texas Health Science Center at San Antonio