VEGF induces expression of Bcl-2 and multiple signaling factors in microvascular endothelial cells in a prostate cancer model

Yoshihisa Sakai, Steve Goodison, Wengang Cao, Virginia Urquidi, Kazunori Namiki, Stacy Porvasnik, Cydney Urbanek, Charles Joel Rosser

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Purpose: 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. Experimental design: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)659-666
Number of pages8
JournalWorld Journal of Urology
Volume27
Issue number5
DOIs
StatePublished - Jun 8 2009

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Keywords

  • Angiogenesis
  • Bcl-2
  • Cancer
  • Gene expression
  • Prostate
  • VEGF

ASJC Scopus subject areas

  • Urology

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