A New Insulin-Like Growth Factor Binding Protein (mac 25) and Its Role in Breast Cancer and Cell Growth Control
Annual rept. 19 Aug 1996-18 Aug 1997
WASHINGTON UNIV SEATTLE
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Mac25 is the seventh member of the IGFBP family IGFBP-7. IGFBP-7 is expressed in normal human mammary epithelial cells HMECs and upregulated in senescent HMECs. IGFBP-7 is not expressed in twelve of sixteen breast cancer cell lines, in studies by two laboratories. Its expression is absent in estrogen receptor positive ER breast cancer cell lines. IGFBP-7 may regulate HMEC growth. We will test the hypothesis that it suppresses growth in ER breast cancer cells. We will also test the ability of IGFBP-7 to negatively affect growth rates in ER breast cancer cells by transducing the cDNA into normal and human breast tumor cultures using a retroviral vector system. We will determine if IGFBP-7 is regulated at the transcriptional level by characterization of the promoter region of the gene. We will determine binding properties of IGFBP-7 protein by gel shift analysis of protein extracts and anti-IGFBP7 antibody. We will determine if IGFBP7 is hormonally regulated by studying tissue specificity of RNA expression and protein localization through in situ hybridization and immunohistochemistry additional aim.
- Anatomy and Physiology
- Medicine and Medical Research