Function of a Novel Signal Transduction Adapter Molecule in Mammary Epithelia
Abstract
A significant fraction of breast cancer cell lines and primary tumors exhibit elevated Src tyrosine kinase activity. The mechanism(s) by which Src kinases become activated is not well understood. In some cases, these enzymes form complexes with various growth factor receptors, leading to their activation. Conceivably other gene products may act in a similar manner. We have cloned a novel adapter-like signaling molecule from epithelial cells that we call SRCASM, for SRC Activating and Signaling Molecule. We hypothesized that elevated expression of SRCASM in mammary epithelia may result in increased Src activation, leading to hyperplasia or transformation. This was explored further by: (1) generation of transgenic mice expressing Srcasm in mammary epithelia. Mice were monitored for changes in mammary gland morphogenesis as well as tumor development; (2) analyze mammary carcinoma cell lines and primary tumor samples to determine whether specific subset of tumors have elevated levels of Srcasm. The relative expression levels were correlated with patient outcome or metastatic phenotype to determine whether monitoring Srcasm expression has any predictive value. We found no correlation between Srcasm expression and either patient outcome or metastatic phenotype. Furthermore the transgenic mice proved uninformative. There was no evidence of accelerated tumor development. This may be due to relative low expression of the transgene. Based on the data accumulated there does not appear to be a significant importance of Srcasm in breast cancer. However, this does not rule out a role in other epithelial cancers. Subsequent reports suggest that Srcasm may be upregulated in cutaneous dysplasias, which may implicate a role for this protein in cutaneous disorders.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA588206
Entities
People
- Paul L. Stein
Organizations
- Northwestern University