Investigations of Functional and Structural Interactions Between c-src and HER2: Involvement in Human Breast Tumor Formation
Abstract
To investigate whether interactions between c-Src and other HER family members may play a role in breast tumor progression, we characterized a panel of thirteen human breast carcinoma cell lines and thirteen tumor samples for expression levels of HER family members and c-Src, and examined a subset of the cell lines for their dependency on Src family members for heregulin (HRU)-augmented, anchorage-dependent growth in reduced serum or colony formation in soft agar. We found that 90-100% of the samples overexpressed one or more HER family members and that c-Src was overexpressed in approximately 70% of the cases. Growth in low serum was potentiated by HRG in five of six cell lines tested (irrespective of HER2/3 or c-Src levels), and colony formation in soft agar was enhanced in only those cell lines that exhibited a c-Src/HER2 heterocomplex, suggesting that physical association between c-Src and HER2 may facilitate HRG-potentiated, anchorage-independent growth. HRG effects were either partially or completely ablated by PP1, a Src family kinase inhibitor. In addition, long-term treatment of adherent cells with PP1 induced apoptosis in all cell lines tested, a process that was significantly reversed by HRG treatment. These data provide the first functional evidence for co-operativity between HRG and Src family kinases in the survival and growth of human breast tumor cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA382883
Entities
People
- Allison P. Belches
- Sarah J. Parsons
Organizations
- University of Virginia