TGFBeta Induction of PMEPA1: Role in Bone Metastasis Due to Prostate Cancer
Abstract
TGFB provided by the bone microenvironment is a key factor in the development of bone metastases. Previous experiments have demonstrated that interference with TGFB signaling in cancer cells decreases the development of bone metastases. TGF BETA stimulates prostate cancer cell signaling and alters their phenotype. TGFB signaling in cancer is however complex and can lead to the activation of numerous genes. We identified PMEPA1 as the most highly unregulated gene by TGF BETA in PC3 cells. Although PMEPA1 has already been shown to be unregulated in different cancers, nothing is known about its function in cells. We have shown that the absence of PMEPA1 in prostate cancer cells decreases TGFB signaling. This result is consistent with preliminary experiments showing that the cytosolic isoform of PMEPA1 which is the most highly expressed in PC3 increases TGFB signaling. Interestingly the other isoforms of PMEPA1 which are membrane bound have an opposite effect, decreasing TGF Beta signaling. These results suggest that depending on which isoform is the most abundant in cells, PMEPA1 can provide a positive or negative feedback loop for TGFB signaling. We are in the process of stably knocking down and over expressing PMEPA1 in PC3 cells to determine the effect of PMEPA1 on bone metastases development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2008
- Accession Number
- ADA491127
Entities
People
- Pierrick G. Fournier
Organizations
- University of Virginia