Accession Number : ADA304456

Title :   Cell Signalling by a Novel SH2 Domain Protein that is Overexpressed with Her2 in Breast Cancer.

Descriptive Note : Annual rept. 1 Dec 94-30 Nov 95,

Corporate Author : NEW YORK UNIV MEDICAL CENTER NY

Personal Author(s) : Margolis, Benjamin L.

PDF Url : ADA304456

Report Date : JAN 1996

Pagination or Media Count : 16

Abstract : We have been studying the role of the SH2 domain protein, Grb7, in breast cancer. Studies completed this year confirmed that Grb7 is overexpressed in almost all tumors that overexpress HER2. We have generated MCF-7 breast cancer cell lines where Grb7 is overexpressed with HER2 and the EGF-Receptor/HER2 chimera. These studies confirm that Grb7 binds strongly to HER2 but overexpression of Orb7 appears to have no effect on the growth of MCF-7 cell lines or their migration in collagen gels. To clarify the role of Grb7, we are now repeating these studies in the non-transformed MCF- 10A cell line that may be more sensitive to the effects of Grb7 overexpression. Other studies have examined proteins that bind to the central region of Grb7 and may be involved in signal transduction. We have identified a protein that binds to this region of Grb7 by screening bacterial expression libraries. However, the physiologic relevance of this protein/protein interaction is unclear and further studies are being performed using bacterially expressed fusion proteins of Grb7 and radioactively labelled cell lysates. We are also generating monoclonal antibodies to Grb7 to better understand Grb7 expression and protein interactions in breast cancer and normal cells.

Descriptors :   *PROTEINS, *CELLS(BIOLOGY), *MAMMARY GLANDS, *BREAST CANCER, INTERACTIONS, BACTERIA, NEOPLASMS, SIGNALS, TRANSDUCERS, MONOCLONAL ANTIBODIES, GELS, LIBRARIES, COLLAGEN.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE