Abstract Title

Hypoxic Condition Alters Wilms' Tumor 1 and Vascular Endothelial Growth Factor Isoform Expression in Leukemia

Abstract

Vascular endothelial growth factor (VEGF) is necessary for angiogenesis and tumor growth, but VEGF splice isoforms have distinct characteristics, with VEGF121 being more diffusible and allowing for more distant angiogenic signaling, and VEGF165 and VEGF189 being found within the cell and the extracellular matrix. Hypoxia (low level of oxygen) induction of VEGF expression depends on transcription factors such as Wilms’ Tumor 1(WT1) and HIF1a. However the mechanism regulating how VEGF isoform levels change in hypoxia is not clear. We hypothesized that in leukemia cells, VEGF and WT1 levels would increase under hypoxic conditions, and that both VEGF 121 and 165 levels should be enhanced. Based on literature review, hypoxia has shown to regulate serine arginine rich protein kinase 1 (SRPK1), a kinase that phosphorylates splicing factors. We asked whether this pathway would control splicing of VEGF isoform levels in leukemia cells. We measured VEGF and WT1 mRNA levels in leukemia cells cultured in a hypoxia chamber with 1% O2 and compared them to those grown under normoxic conditions. Quantitative real-time PCR analysis was performed to analyze total VEGF, VEGF 121, VEGF 165, and WT1 mRNA expression. Expression was confirmed by examining protein levels using western blotting. Our findings suggest that hypoxia consistently increased both VEGF and WT1 in myeloid and lymphoid derived leukemia cells. However, changes in VEGF isoform levels were cell specific. These results shed light on the hypoxia pathway and indicate that effective anti-angogenic therapy will need to be tailored for each type of leukemia.

Modified Abstract

Vascular endothelial growth factor (VEGF) is necessary for angiogenesis and tumor growth but VEGF splice isoforms have distinct characteristics, with VEGF121 being more diffusible and VEGF165 being found within cell extracellular matrix. Hypoxia induction of VEGF expression depends on transcription factors such as Wilms’ Tumor 1(WT1) and HIF1a, but the mechanism regulating how VEGF isoform levels change is not clear. We hypothesized that in leukemia cells, VEGF, VEGF121, VEGF165 and WT1 levels would increase under hypoxic conditions. Our findings suggest that hypoxia consistently increased both VEGF and WT1 in leukemia cells and changes in VEGF isoform level was cell specific. These results shed light on the hypoxia pathway and indicate that effective anti-angogenic therapy will need to be tailored for each type of leukemia.

Research Category

Biology/Ecology

Primary Author's Major

Biology

Mentor #1 Information

Dr. Gail Fraizer

Mentor #2 Information

Sony Pandey

Presentation Format

Poster

Start Date

March 2016

References.pdf (5 kB)
Reference list

IMG_7422.JPG (1497 kB)
Photo

Biographical sketch.docx (10 kB)
Biographical Sketch

Research Area

Cancer Biology

This document is currently not available here.

Share

COinS
 
Mar 15th, 1:00 PM

Hypoxic Condition Alters Wilms' Tumor 1 and Vascular Endothelial Growth Factor Isoform Expression in Leukemia

Vascular endothelial growth factor (VEGF) is necessary for angiogenesis and tumor growth, but VEGF splice isoforms have distinct characteristics, with VEGF121 being more diffusible and allowing for more distant angiogenic signaling, and VEGF165 and VEGF189 being found within the cell and the extracellular matrix. Hypoxia (low level of oxygen) induction of VEGF expression depends on transcription factors such as Wilms’ Tumor 1(WT1) and HIF1a. However the mechanism regulating how VEGF isoform levels change in hypoxia is not clear. We hypothesized that in leukemia cells, VEGF and WT1 levels would increase under hypoxic conditions, and that both VEGF 121 and 165 levels should be enhanced. Based on literature review, hypoxia has shown to regulate serine arginine rich protein kinase 1 (SRPK1), a kinase that phosphorylates splicing factors. We asked whether this pathway would control splicing of VEGF isoform levels in leukemia cells. We measured VEGF and WT1 mRNA levels in leukemia cells cultured in a hypoxia chamber with 1% O2 and compared them to those grown under normoxic conditions. Quantitative real-time PCR analysis was performed to analyze total VEGF, VEGF 121, VEGF 165, and WT1 mRNA expression. Expression was confirmed by examining protein levels using western blotting. Our findings suggest that hypoxia consistently increased both VEGF and WT1 in myeloid and lymphoid derived leukemia cells. However, changes in VEGF isoform levels were cell specific. These results shed light on the hypoxia pathway and indicate that effective anti-angogenic therapy will need to be tailored for each type of leukemia.