| First Author | Conley-LaComb MK | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 3 | Pages | 1017-27 |
| PubMed ID | 22209699 | Mgi Jnum | J:181962 |
| Mgi Id | MGI:5314477 | Doi | 10.1016/j.ajpath.2011.11.021 |
| Citation | Conley-LaComb MK, et al. (2012) PTEN regulates PDGF ligand switch for beta-PDGFR signaling in prostate cancer. Am J Pathol 180(3):1017-27 |
| abstractText | Platelet-derived growth factor (PDGF) family members are potent growth factors that regulate cell proliferation, migration, and transformation. Clinical studies have shown that both PDGF receptor beta (beta-PDGFR) and its ligand PDGF D are up-regulated in primary prostate cancers and bone metastases, whereas PDGF B, a classic ligand for beta-PDGFR, is not frequently detected in clinical samples. In this study, we examined the role of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in the regulation of PDGF expression levels using both a prostate-specific, conditional PTEN-knockout mouse model and mouse prostate epithelial cell lines established from these mice. We found an increase in PDGF D and beta-PDGFR expression levels in PTEN-null tumor cells, accompanied by a decrease in PDGF B expression. Among Akt isoforms, increased Akt3 expression was most prominent in mouse PTEN-null cells, and phosphatidylinositol 3-kinase/Akt activity was essential for the maintenance of increased PDGF D and beta-PDGFR expression. In vitro deletion of PTEN resulted in a PDGF ligand switch from PDGF B to PDGF D in normal mouse prostate epithelial cells, further demonstrating that PTEN regulates this ligand switch. Similar associations between PTEN status and PDGF isoforms were noted in human prostate cancer cell lines. Taken together, these results suggest a mechanism by which loss of PTEN may promote prostate cancer progression via PDGF D/beta-PDGFR signal transduction. |
