A Molecular Approach for Metastatic Progression of Breast Cancer
Abstract
Heregulin (HRG) and HER2/neu signaling pathways play an important role in the progression of breast tumors to a more motile phenotype. Cell motility I adhesion is also controlled by Focal adhesion kinase (FAK), which is also over expressed in breast tumors. To explore the molecular participation of FAK in HRG and HER2- signaling, we characterized the pattern of activation of FAK, Src and paxillin, all components of functional focal adhesion complex using phosphospecific antibodies. In breast cancer cell line MCF-7, HRG differentially regulate Tyr-phosphorylation of FAK, paxillin and c-Src in a dose dependent manner. At low dose, HRG induced Tyr phosphorylation FAK at Tyr 577, 925, 405 while at higher dose HRG induced selective dephosphorylation of FAK at Tyr 577, 925, 405. Interestingly, HRG at higher dose induced phosphorylation of FAK at Tyr-861 and Src at Tyr-215 . We conclude that HER2, HRG system differentially regulate signaling from FAK by selectively dephosphorylating or activating some tyrosine residues and thus increase their migratory potential rather than adhesion. Phosphospecific antibodies against FAKTyr-861 and Src Tyr-215 may potentially be used as an effective reagent to screen I identifying the putative metastatic/motile potential of breast tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407418
Entities
People
- Ratna K Vadlamudi
Organizations
- The University of Texas MD Anderson Cancer Center