A Role for TIMP-1 in Breast Cancer Progression
Abstract
The studies in this grant are designed to assess the role of TIMP-1 in invasion and metastasis with emphasis on the Ras signaling pathway. We have previously provided evidence that TIMP-1 may induce epithelial to mesenchymal transition in MCF 10A cells. In order to further assess the role of TIMP-1 in breast cancer development, we created several MCF-7 cell lines which overexpress TlMP-1. Using low, medium and high overexpressing clones we determined that high levels of TIMP-1 are directly correlated with expression of VEGF. Interestingly, TIMP-1 had no effect on proliferation of MCF-7 cells. In addition, the TIMP-1 clones demonstrated no difference in invasion compared to vector control cells. it was observed by immunofluorescence that TIMP-1 overexpressing clones had a significantly higher number of multi-nucleated cells. Studies are underway to assess the cause of this phenomenon. We are currently assessing downstream signaling affected by TlMP-1 overexpression. We have observed no changes in FAK activation but increases in the MAPK pathway. Using cytokine protein arrays, we have observed expression changes in several cytokines in the TIMP-1 overexpressing clones, including CSF-1, IL-1O and IGFBP-2. We are currently confirming these results. We have also begun in vivo studies by injecting the MCF-7 vector control and 3 clones with varying TIMP-1 levels into mouse mammary fat pads. Results are expected in approximately a month. These combined results provide further evidence that TIMP-1 has a role in tumorigenesis other than inhibition of MMPs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA443772
Entities
People
- James A. Cardelli
- Rebecca Bigelow
Organizations
- Louisiana State University