A New Insulin-Like Growth Factor Binding Protein (mac25) and Its Role in Breast Cancer and Cell Growth Control
Abstract
Mac25 is the first member of the IGFBP-rP family (IGFBP-rP1). IGFBP-rP1 is expressed in normal human mammary epithelial cells (HMECs) and upregulated in senescent HMECs. IGFBP-rP1 is not expressed in twelve/sixteen breast cancer cell lines and its expression is absent in estrogen receptor positive (ER+) breast cancer cell lines. IGFBP-rP1 may regulate HMEC growth. We tested the hypothesis that it suppresses growth in ER+ breast cancer cells by transducing the cDNA into normal and human breast tumor cultures. We will determine if IGFBP-rP1 is regulated at the transcriptional level by characterization of the promoter. We have determined binding properties of IGFBP-rP1 by growth assays in presence of IGF-I, IGF-II, R3-IGF-I, and R6-IGF-II and immunoprecipitation/phosphatase assays. We have determined IGFBP-rP1 tissue specificity by mRNA in situ hybridization. We have ascertained that IGFBP-rP1 negatively regulates growth in ER+ breast cancer cells. IGFBP- rP1 blocks growth stimulation by insulin, EGF, and IGF-II. Experiments indicate IGFBP-rP1 binds IGF-II. IGFBP-rP1 generated in ER+ breast cancer cells exhibit two bands of higher molecular weight compared to protein found in ER breast cancer cells. We have isolated one clone from a library screen that contains approximately 1kb of sequence 5' of the translation start site.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADB240160
Entities
People
- Karan Swisshelm
Organizations
- University of Washington