Different effects of glucose starvation on expression and stability of VEGF mRNA isoforms in murine ovarian cancer cells.
Vascular endothelial growth factor (VEGF) has been implicated as a potent regulator of angiogenesis in tumors, and its protein exists as at least five isoforms with distinct biologic activities and clinical significance. Tumors under metabolic stress conditions dramatically increase VEGF expression due to both increased transcription and decreased mRNA degradation. However, it is not known how stress conditions regulate expression of each VEGF isoform. Here, we report a novel Taqman real-time RT-PCR strategy for quantification of all murine VEGF isoforms and find that (1) glucose starvation dramatically up-regulates the mRNA level of all VEGF isoforms, with the three abundant isoforms, VEGF120, VEGF164, and VEGF188, increasing at a similar rate, while the rare isoform VEGF144 is more markedly up-regulated; (2) glucose starvation induces a significant increase of the relative abundance of VEGF144 mRNA, but not the more prevalent isoforms VEGF120, VEGF164, and VEGF188, compared to total VEGF; and (3) the stability of each isoform mRNA differs under the control conditions as well as glucose starvation. The latter significantly stabilizes mRNA of all VEGF isoforms at a different rate, with VEGF144 most significantly stabilized. Our results indicate that under metabolic stress conditions VEGF144 is the most dramatically up-regulated VEGF isoform, probably through mechanism(s) different from the three abundant VEGF isoforms.
Zhang
Lin
L
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Conejo-Garcia
Jose-Ramon
JR
Yang
Nuo
N
Huang
Wei
W
Mohamed-Hadley
Alisha
A
Yao
Weijia
W
Benencia
Fabian
F
Coukos
George
G
D017398:Alternative Splicing; D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism* / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000187:drug effects / Q000502:physiology*; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D012334:RNA, Neoplasm; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005947:Glucose