Bioavailability of TGF-Beta in Breast Cancer
Abstract
Radiation elicits rapid and persistent changes in the mouse mammary microenvironment, and persistent transforming growth factor-beta (TGF-beta) activation. TGF-beta has widely diverse functions in regulation of proliferation and cell fate-decisions, which contribute to a variety of tissue processes. TGF-beta super family includes three mammalian isoforms (beta1, beta2, and beta3) that are secreted in a latent complex formed by non-covalent association with the relevant latency-associated peptide (LAP1, LAP2, or LAP3). Mouse models utilizing protein knockout protocols reveal that the three isoforms have distinctly different roles in the cellular pathway, as seen by the mouse phenotypes. Activation of TGF-beta involves dissociation of this complex and perhaps degradation of LAP. However the mechanism and mode of activation is poorly understood. We postulate that the presence of metals in the latent complex could provide a redox active center for this process. Given the LAP sequence differences we hypothesized that redox-mediated activation will be isoform specific. Redox mediated activation offers a novel route for TGF-beta1 involvement in chronic tissue processes in which oxidative stress is implicated and would endow LTGF-beta1 with the ability to both sense extracellular oxidative stress and transduce the signal by eliciting changes in diverse cell types.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA429598
Entities
People
- Michael F. Jobling
Organizations
- University of California, Berkeley