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

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World Journal of Urology Aims and scope Submit manuscript

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.

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Abbreviations

VEGF:

Vascular endothelial growth factor

Bcl-2 :

B-cell CLL/lymphoma 2

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Conflict of interest statement

None.

Author information

Authors and Affiliations

  1. Department of Urology, University of Florida College of Medicine, PO Box 100247, Suite N215, Gainesville, FL, 32610, USA

    Yoshihisa Sakai, Wengang Cao, Kazunori Namiki, Stacy Porvasnik, Cydney Urbanek & Charles Joel Rosser

  2. Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA

    Charles Joel Rosser

  3. Department of Surgery, University of Florida, Jacksonville, FL, USA

    Steve Goodison

  4. Department of Medicine, University of Florida, Jacksonville, FL, USA

    Virginia Urquidi

Authors
  1. Yoshihisa Sakai
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  2. Steve Goodison
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  3. Wengang Cao
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  4. Virginia Urquidi
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  5. Kazunori Namiki
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  6. Stacy Porvasnik
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  7. Cydney Urbanek
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  8. Charles Joel Rosser
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Corresponding author

Correspondence to Charles Joel Rosser.

Additional information

Y. Sakai and S. Goodison are co-first authors.

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Sakai, Y., Goodison, S., Cao, W. et al. VEGF induces expression of Bcl-2 and multiple signaling factors in microvascular endothelial cells in a prostate cancer model. World J Urol 27, 659–666 (2009). https://doi.org/10.1007/s00345-009-0422-0

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  • DOI: https://doi.org/10.1007/s00345-009-0422-0

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