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Immunobiological Aspects of erbB Receptors in Breast Cancer.

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Annual rept. 15 Jul 97-14 Jul 98

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Our work is concerned with the erbB-2neu family of receptors. The purpose of these studies was to provide information on the role of the endodomain in signalling and endocytosis of the receptor complex. In addition, we wished to identify, molecularly, ligands that would specifically bind to and activate the neu receptor. We have significantly increased our understanding of how the p185neu endodomain associates with and contributes to EGFR-p185 heteromeric receptor signalling and endocytosis. We used a variety of molecular mutants and chimeras EGFR ectodomain and neu transmembrane and endodomain to characterize specific residues and subdomains of the endodomain responsible for discrete activities. In addition, we have used an oligonucleotide probe derived from the transmembrane sequence of erbB-3 and 4 ligands to screen an ATL-2 cDNA library and have identified novel ligand sequences that potentially may represent an authentic p185neu ligand. These sequences will be used to identify a full length cDNA sequence that will be tested for biological activity in vitro and in vivo. The significance of these findings is that they provide new insights into the structure and behavior of this receptor family and its ligands in normal cell growth and breast cancer development.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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