Transforming Growth Factor-B Receptors in Human Breast Cancer.
Abstract
This project addresses the question whether and, if so, how molecular lesions of the genes involved in the TGFB signaling pathway contribute to the origin and/or progression of breast cancer. We have cloned and determined the intron-exon structure of the TGFB type I receptor (TBR-I). This has allowed us to study this gene in a series of primary breast cancer specimens. Our most important finding is a much higher frequency of an exon 1 receptor variant among breast cancer cases than controls. Secondly, we have identified a serine to tyrosine mutation within the catalytic core of the TBR-I serine-threonine kinase domain in 2 of 31 primary and 5 of 12 metastatic breast cancer specimens. Thirdly, we have developed transient transfection as says to determine how specific TBR mutations affect receptor function. Using these assays we have shown that two previously identified TBR-II missense mutants are incapable of signaling because of the near complete loss of receptor kinase activity. Plans for the coming year include completing structural analyses of the TBR-I and -II genes in primary and metastatic breast cancer and defining the functional properties of the newly discovered TBR-I variant and mutant.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1998
- Accession Number
- ADA349599
Entities
People
- Michael Reiss
Organizations
- Yale University