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-rPl). IGFBP-rpl is expressed in normal human mammary epithelial cells (HMECs) and upregulated in senescent HMECs. IGFBP-rPl 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-rPl may regulate HMEC growth. We tested the hypothesis that IGFBP-rPl suppresses growth in ER+ breast cancer cells by transducing the cDNA into normal and human breast tumor cultures. IGFBP-rpl negatively regulates growth in ER+ breast cancer cells. Growth inhibition is independent of apoptotic regulatory pathways. We observed an initial change in cell morphology to a senescent phenotype. IGFBP-rPl may inhibit growth through senescence-associated pathways. IGFBP-rPl secreted by ER+ breast cancer cells exhibit two higher molecular weight proteins compared to protein secreted by ER- breast cancer cells. We were unable to determine the binding properties of IGFBP-rP1 by growth assays in presence of IGF-I, IUF-II, R3-IGF-I, and R6-IGF-II. We have detected cell-specific and gender-specific differences of IGFBP-rPl mRNA expression in male and female C57BL6 mice suggesting that IGFBP-rPl may be hormonally regulated. We would like to determine regulation of IGFBP-rPl at the transcriptional level by characterization of the promoter and have isolated two potential clones from a genomic library screen that may contain the 5'end of IGFBP-rPl and a portion of the promoter sequence.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADB264626
Entities
People
- Heather-marie P. Wilson
- Karen Swisshelm
Organizations
- University of Washington