Decreased production of vascular endothelial growth factor in adriamycin-resistant breast cancer cells

Jung Ae Kim, Kyoung Bin Cho, Mi Ra Kim, Byung Chul Park, Sang Kyum Kim, Moo Yeol Lee, Keon Wook Kang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

MCF-7/ADR cells, a doxorubicin-resistant human breast cancer cell line, have acquired resistance to several anti-cancer chemotherapeutic agents, such as anthracyclines and taxol. Here, we found that MCF-7/ADR cells produced lower levels of vascular endothelial growth factor (VEGF) than control MCF-7 cells. Molecular analyses using Western blots and reporter constructs containing either the human VEGF promoter or a minimal promoter for the transcription factor, hypoxia-inducible factor-1 (HIF-1), supported the involvement of HIF-1α in the down-regulation of VEGF transcription in MCF-7/ADR cells. In addition, the basal activities of Akt and GSK-3β were deregulated in MCF-7/ADR cells, and either the activation of PI3-kinase or the inhibition of GSK-3 restored the diminished transcription of VEGF. Chick chorioallantoic membrane (CAM) assay finally confirmed that angiogenesis intensity in MCF-7/ADR cells was significantly decreased compared with that in control MCF-7 cells.

Original languageEnglish
Pages (from-to)225-232
Number of pages8
JournalCancer Letters
Volume268
Issue number2
DOIs
StatePublished - 18 Sep 2008

Keywords

  • Adriamycin-resistant breast cancer
  • Angiogenesis
  • HIF-1α
  • VEGF

Fingerprint

Dive into the research topics of 'Decreased production of vascular endothelial growth factor in adriamycin-resistant breast cancer cells'. Together they form a unique fingerprint.

Cite this