Regulation of Growth Factor Release by Protease Inhibitors in Breast Cancer
Abstract
Epithin, a potential TGF alpha cleaving enzyme has been cloned from MCF-7 breast cancer cells. The cDNA has a deduced 855 amino acid sequence consistent with that of a multi-domain type II membrane protease. Epithin shows both membrane spanning and serine protease domains. It also has putative CUB and LDRA domains which may be important for regulation and/or substrate binding. Northern blotting showed highest expression in epithelial cells particularly breast and kidney. Epithin antibodies blocked release of TGF alpha from MCF-7 cells suggesting that epithin may be involved proTGF alpha processing. Incubation of MCF-7 cells with the metalloprotease inhibitor BB-3103 blocked epithin processing suggesting a metalloprotease may needed for epithin activation. Membrane fractions from MCF-7 cells incubated with a labeled serine protease inhibitor showed a 33 kDa labeled band, which was recognized by the epithin antibody. Epithin also shows gelatinase activity suggesting that it may be directly involved in invasion. Immunohistochemistry of paraffin sections from normal human breast tissue showed that the epithin protein was restricted to the surface of ductal epithelial cells where it co-localized with the epidermal growth factor receptor. Epithin expression appeared to be elevated in DCIS and in invasive breast carcinoma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA379053
Entities
People
- Thomas H. Finlay
Organizations
- NYU Langone Health