The Cellular Localization of IGFBP5 Determines its Oncogenic Functions in Breast Cancer
Abstract
We established an IGFBP5 mutant in the nuclear localization motif and breast cancer cell lines that stably express the mutants as well as wild type form. We have constructed fluorescent fusion protein (pDsRed) with both wt IGFBP5 and nuclear localization signal mutant IGFBP5 and evaluated their cellular localization. We also evaluated cellular localization of the untagged forms of these two proteins. We found that mutation of the nuclear localization signal altered the IGFBP5 localization from nucleus to being secreted outside the cells. Further the secreted form of IGFBP5 is resistant of a cleavage activity. We studied the behavior of the mutant IGFBP5 in two assays: DNA synthesis and cell migration. We found that in contrast to wild-type IGFBP5 which inhibits DNA synthesis and cell migration mutant IGFBP5 promotes DNA synthesis and cell migration. These results support our hypothesis that localization of IGFBP5 determines its cellular function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA457676
Entities
People
- Wei Zhang
Organizations
- The University of Texas MD Anderson Cancer Center