Format

Send to

Choose Destination
See comment in PubMed Commons below
Oncogene. 2011 Mar 10;30(10):1205-12. doi: 10.1038/onc.2010.496. Epub 2010 Nov 8.

Intracrine vascular endothelial growth factor signaling in survival and chemoresistance of human colorectal cancer cells.

Author information

  • 1Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA.

Abstract

Although the effects of vascular endothelial growth factor (VEGF) on angiogenesis and vascular function are well known, the effects of VEGF on tumor cell function remain to be elucidated. We studied phenotypic changes in human colorectal cancer (CRC) cells with homozygous deletion of VEGF alleles to determine the potential direct role of VEGF on tumor cell function. Loss of VEGF expression led to significantly decreased cell growth and increased spontaneous apoptosis in CRC cells (P<0.01). Loss of VEGF also increased the in vitro sensitivity of cells to the cytotoxic effects of the chemotherapeutic drug 5-fluorouracil, as shown by increased apoptosis (P<0.05). These effects were mediated via upregulation of the proapoptotic mediators caspase-3, cleaved PARP and Bax and downregulation of the pro-survival mediator survivin. Our findings suggest a novel and distinct function of VEGF in mediating autocrine/intracrine CRC cell survival.

PMID:
21057529
PMCID:
PMC3224802
DOI:
10.1038/onc.2010.496
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center