Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in many pathological processes. We investigated the regulation of 4 alternatively spliced isoforms (121, 165, 189 and 206 amino acids) by hypoxia, hypoglycemia, acidity, female reproductive hormones and vitamin D in breast carcinoma cell lines representing different tumor phenotypes. There was a 17-fold difference in total VEGF mRNA expression across the cell lines. The isoform expression, 121 > 165 > 189, was unchanged by different culture conditions. Hypoxia was the most potent stimulus, and the cell lines demonstrated a 1.4- to 6.9-fold range of VEGF induction, maintained when other hypoxically regulated genes (phosphoglycerate kinase 1 and glucose transporter 1) and a HIF-1-dependent reporter gene were examined. The relative inducibility of the genes was maintained in each cell line, but basal expression was independent of -fold induction. VEGF expression decreased under acidic conditions in 2 cell lines, but the hypoxia stimulus remained effective under acidic conditions. Hypoglycemia, female reproductive hormones and vitamin D exerted no effect on expression, nor did inhibitors of mutant ras. Our results show that VEGF expression varies widely between cell lines and that capacity to respond to hypoxia is also cell specific, relating mostly to the hypoxic sensing of the cell and the signal transduction mechanism. Such characteristics, if maintained in vivo, have implications for the angiogenic potential of different tumor cells under normal and hypoxic conditions.

Original publication

DOI

10.1002/(sici)1097-0215(19980302)75:5<706::aid-ijc8>3.0.co;2-2

Type

Journal article

Journal

Int J Cancer

Publication Date

02/03/1998

Volume

75

Pages

706 - 712

Keywords

Breast Neoplasms, Calcitriol, DNA-Binding Proteins, Endothelial Growth Factors, Endothelium, Vascular, Estrogens, Female, Gene Expression Regulation, Neoplastic, Humans, Hydrogen-Ion Concentration, Hypoxia, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Lymphokines, Nuclear Proteins, Progesterone, RNA, Messenger, RNA, Neoplasm, Transcription Factors, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors