Role of Tumor Microenvironment and the FGF Signaling Axis on Differentiation and Emergence of the Neuroendocrine Phenotype in Prostate Cancer
Abstract
Specific changes in the fibroblast growth factor (FGF) signaling axis can abrogate stromal-epithelial interactions to modify the microenvironment of the prostate gland. We have previously demonstrated that signaling through ECK receptor 1 (FGFR1) but not FGFR2 promoted emergence of epithelial to neuroendocrine transition (ENT) . We have established protocols to introduce constitutively active receptors in prostate epithelial cells and measure expression of genes associated with epithelial (E-cadherin), stromal (Cadherin- 11), neuronal (N-cadherin), angiogenic (VE-cadherin), and neuroendocrine (neuron-specific enolase, chromogranin A, and synaptophysin) phenotypes using Real-Time PCR. In determined that TRAMP-C2H, known to be tumorigenic and metastatic, express high levels of FGFRliiic in contrast to ClA cells that are not tumorigenic. Consistent with clinical data C2H cells express very low levels of E-cadherin (<1%) when compared to intact mouse prostate. Whereas normal mouse prostate does not express N-cadherin, C2H cells were found to express almost a 1000-fold higher level than ClA and expression of VE-cadherin in C2H was only ^1% that of mouse prostate. Interestingly, C2H cells express high levels of Slug, an E-box transcription factor implicated in negative regulation of differentiation-specific markers such as E-cadherin. Ongoing studies are aimed to elucidate the downstream molecular mechanisms that drive emergence of the neuroendocrine phenotype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA435446
Entities
People
- Andreas I. Evangelou
Organizations
- Baylor College of Medicine