TGFB1 Regulation of Matrix Metalioproteinase-9 in Human Prostate Cancer Metastasis
Abstract
Matrix metalloproteinases (MMPs) facilitate invasion, growth factor activation, proliferation and angiogenesis during prostate cancer progression and are a target for anti-metastatic agents. Existing inhibitors of MMPs (MMPIs) such as COL-3 and Prinomastat used in prostate cancer clinical trials are synthetic molecules and suffer from dose- limiting toxicities or lack of efficacy. This New Investigator research pursued an alternative course of MMP inhibition by studying growth factor-induced secretion of MMP-9 by TGF Beta 1 in prostate cancers. Both MMP-9 and TGF Beta 1 are clinically and experimentally associated with prostate cancer metastasis. TGF Beta 1 upregulates cancer cell MMP-9 by mRNA stabilization. Since mRNA stability is usually regulated through binding proteins, we expressed fragments of the 3'UTR to determine if one or more fragment would be responsible for TGF Beta 1 effects on mRNA half-life. We also began to use our MMP-9 3'UTR deletion constructs in vitro in cell lines and in vitro invasion as says to measure MMP-9 expression and inhibition of invasion as end points. Our attempts to test sequences for TGF Beta 1- induced or repressed protein associations and identify such proteins are ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA430453
Entities
People
- Jaqdish Singh
Organizations
- North Dakota State University