Int-3 Oncogene in Normal and Neoplastic Breast Development.
Abstract
Mutational activation of the murine int-3 oncogene can contribute to mammary gland tumorigenesis. Evidence suggests that int-3 regulates the morphogenesis and functional differentiation of the mouse mammary gland. The proposed research investigates the role of int-3 proteins in the normal physiology of braast development and the biochemical properties critical for mt-3 transforming activity. cDNAs encoding the truncated int-3 oncogene were cloned. A full length cDNA of approximately 7.3 kilobases was subsequently cloned and has been sequenced. The deduced amino acid sequence verifies that int-3 is a Notch/lin-12 family member. Structually, the int-3 protein contains approximately 20 EGF-like repeats, 3 Notch/lin-12 repeats, a transmembrane domain, and an intracellular domain containing six ankyrin repeats. Analysis of int-3 mRNA shows expression in several adult tissues and during mouse embryonic development. Cell lines have been generated that express an epitope-tagged int-3 oncoprotein, which was detected by Western blot and immunofluorescence analysis. Activated int-3 oncoproteins were found primarily in the nucleus and putative nuclear localization signals have been identified. Finally, bacterially produced int-3 proteins have been purified and used to generate rabbit polyclonal serum.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1995
- Accession Number
- ADA302124
Entities
People
- Jan Kitajewski
Organizations
- Columbia University