TGFB1 Regulation of Matrix Metalioproteinase-9 in Human Prostate Cancer Metastasis
Abstract
Matrix Metalloproteinases (MMPs) facilitate invasion, growth factor activation, and angiogenesis during the metastasis of prostate cancer and they have become a popular target for anti-metastasis agents. Existing anti- MMP drugs are synthetically designed pharmacologic antagonists with a relatively broad spectrum of action and clinical toxicities which have proven unacceptable. This New Investigator research pursues an alternative approach to these toxic chemicals. We focus on one MMP--MMP-9 because it is clinically linked with prostate cancer metastasis and can be induced from very low to high levels in prostate cancer cells by TGFbeta1, which is itself clinically and experimentally associated with prostate cancer metastasis. We are attacking the proteinase at the level of transcription. Transcriptional upregulation of MMP-9 by TGFBETA1 involves an enhancement of the stability of the MMP-9 mRNA molecules. Understanding how this increased mRNA stability occurs is our project's goal. We are attempting to identify new targets on the MMP-9 transcript protected by the induction or repression of RNA-binding proteins induced by TGFBETA1. We are also attempting to isolate and attempt to identify these TGFBETA1-regulated proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA398050
Entities
People
- Inder Sehgal
Organizations
- North Dakota State University