Back to Search
Start Over
VEGF induces expression of Bcl-2 and multiple signaling factors in microvascular endothelial cells in a prostate cancer model
- Publication Year :
- 2009
-
Abstract
- We have previously demonstrated that prostate tumors that highly express Bcl-2 are not only more tumorigenic, but also more angiogenic than low Bcl-2 expressing tumors. Observed increased rates of angiogenesis are likely due to the secretion of multiple factors from the tumor cells.Human endothelial cells were subjected to exogenous VEGF or conditioned media from PC-3 cells and assayed by several in vitro systems to better characterize the effects of tumor microenvironment on endothelial cells.VEGF stimulation increased Bcl-2 expression in human microvascular endothelial cells (HMVECs), at least partially through stabilization of Bcl-2 mRNA transcripts, and protected these cells from apoptosis. These effects were mimicked by treatment of HMVECs with conditioned media from cultured PC-3 prostate tumor cells manipulated to overexpress Bcl-2. Through the use of kinase inhibitors and molecular profiling, several distinct pathways were implicated in the regulation of Bcl-2 in HMVECs, including those involving PI3K/AKT, PKC, mTOR, STAT-1, and IL-8, factors associated with tumor survival and growth.This study identifies molecular elements of a link between Bcl-2 expression in distinct cell types within a tumor and reaffirms that strategies designed to target Bcl-2 are desirable as they might enhance treatment response through dual effects.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Endothelium
Angiogenesis
Urology
Article
Neovascularization
Prostate cancer
Prostate
Tumor Cells, Cultured
Medicine
Humans
business.industry
Cancer
Prostatic Neoplasms
medicine.disease
Endothelial stem cell
Gene Expression Regulation, Neoplastic
Vascular endothelial growth factor A
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Microvessels
Cancer research
Endothelium, Vascular
medicine.symptom
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7f76a805059014e71b85e44de0084c20