PMID- 18471962 OWN - NLM STAT- MEDLINE DCOM- 20081014 LR - 20131121 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 268 IP - 2 DP - 2008 Sep 18 TI - Decreased production of vascular endothelial growth factor in adriamycin-resistant breast cancer cells. PG - 225-32 LID - 10.1016/j.canlet.2008.03.050 [doi] AB - 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-1alpha in the down-regulation of VEGF transcription in MCF-7/ADR cells. In addition, the basal activities of Akt and GSK-3beta 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. FAU - Kim, Jung-Ae AU - Kim JA AD - College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. FAU - Cho, Kyoung Bin AU - Cho KB FAU - Kim, Mi Ra AU - Kim MR FAU - Park, Byung Chul AU - Park BC FAU - Kim, Sang Kyum AU - Kim SK FAU - Lee, Moo Yeol AU - Lee MY FAU - Kang, Keon Wook AU - Kang KW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080508 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - 80168379AG (Doxorubicin) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) SB - IM MH - Antibiotics, Antineoplastic/*pharmacology MH - Breast Neoplasms/blood supply/*drug therapy/metabolism MH - Cell Line, Tumor MH - Doxorubicin/*pharmacology MH - Drug Resistance, Neoplasm MH - Female MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/physiology MH - Neovascularization, Pathologic/prevention & control MH - Phosphatidylinositol 3-Kinases/physiology MH - Promoter Regions, Genetic MH - Vascular Endothelial Growth Factor A/*biosynthesis/genetics EDAT- 2008/05/13 09:00 MHDA- 2008/10/15 09:00 CRDT- 2008/05/13 09:00 PHST- 2008/01/21 00:00 [received] PHST- 2008/03/27 00:00 [revised] PHST- 2008/03/28 00:00 [accepted] PHST- 2008/05/13 09:00 [pubmed] PHST- 2008/10/15 09:00 [medline] PHST- 2008/05/13 09:00 [entrez] AID - S0304-3835(08)00258-9 [pii] AID - 10.1016/j.canlet.2008.03.050 [doi] PST - ppublish SO - Cancer Lett. 2008 Sep 18;268(2):225-32. doi: 10.1016/j.canlet.2008.03.050. Epub 2008 May 8.