Regulation of Neu Signaling in Breast Cancer
Annual rept. 1 JUl 96-30 Jun 97
YALE UNIV NEW HAVEN CT
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ERBB-2neu amplification and overexpression is the most common genetic alteration in breast cancer. As a growth factor receptor and member of the EGFR family, erbB-2 signaling is dependent upon target tissue expression of erbB-2 regulating growth factors and other EGFR family members. To determine the role erbB-2 plays in malignant mammary gland development I examined expression of each EGFR family member and their ligands during normal development of the mouse mammary gland. I found that each receptor is expressed throughout mammary gland development. In contrast, mammary gland expression of the erbB-2 agonists AR and HRG is developmentally regulated - AR being expressed in virgin mice and HRG expressed during pregnancy. This result suggested that erbB-2 agonists may drive mammary gland development. To test this hypothesis I implanted pellets containing HRG within mammary glands of virgin mice. I found that HRG could induce differentiation of mammary epithelium in this system. I predict that erbB-2 expressing breast tumor cells may be induced to differentiate by amplifying the HRG signaling pathway in these cells. I am currently designing experiments in an attempt to decipher the HRG signaling pathway.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research