Inhibition of NF-kappaB activity decreases the VEGF mRNA expression in MDA-MB-231 breast cancer cells.
VEGF (vascular endothelial growth factor) secreted from tumor cells including breast cancer serves as a potent angiogenic factor which favors tumor growth and metastasis. Indeed, a higher concentration of serum VEGF has been shown to associate with a poorer prognosis in patients with breast cancer. On the other hand, constitutive expression of a transcription factor, NF-kappaB was correlated with progression and metastasis in a number of human breast cancers, suggesting a possible regulation of VEGF expression by NF-kappaB. We thus investigated the relationship between the expression of VEGF and constitutive NF-kappaB activity in three breast cancer cell lines, MCF-7, T47D, and MDA-MB-231. The basal levels of VEGF mRNA expression correlated with those of nuclear NF-kappaB activity in these cell lines. The highest NF-KB activity in MDA-MB-231 cells was associated with the highest expression of VEGF mRNA, while the activity and the mRNA levels were moderate in MCF cells and the lowest in T47D cells. In MDA-MB-231 cells, inhibition of NF-KB by adenovirus-mediated expression of a dominant negative NF-kappaB or by a proteasome inhibitor, MG132, decreased the VEGF mRNA. These results suggest that NF-kappaB is involved in the upregulation of VEGF mRNA and inhibition of the activity could be a new approach for the treatment of breast cancer by preventing angiogenesis.
Shibata
Arihiro
A
Department of Endocrinology and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Japan.
Nagaya
Takashi
T
Imai
Tsuneo
T
Funahashi
Hiroomi
H
Nakao
Akimasa
A
Seo
Hisao
H
D001943:Breast Neoplasms / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000494:pharmacology*; D016328:NF-kappa B / Q000494:pharmacology*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D016328:NF-kappa B; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors