Regulation of Angiogenesis and Tumor Growth by p110 Alpha and AKT1 via VEGF Expression

Details

• Personal Author:
  Ca ZX ; Jiang BH ; Meng Q ; Shi XL ; Xia C
• Description:
  Recent studies demonstrate that PI3K activation and PTEN mutation are frequently found in many human cancer cells and tissues. However, the mechanism of PI3K signaling in human cancer tumorigenesis remains to be elucidated. In this study we specifically downregulated p110alpha expression in ovarian cancer cells using siRNA interference. We found that p110alpha downregulation greatly decreased ovarian tumor growth and angiogenesis, and that p110alpha siRNA inhibited VEGF expression through decreasing hypoxia-inducible factor 1alpha expression in both ovarian cancer cells and tumor tissues. To determine the downstream targets of PI3K in regulating tumor growth and angiogenesis, we find that AKT1 is a major downstream mediator for regulating tumor growth, angiogenesis, and VEGF expression. These data show that p110alpha and AKT1 play an important role in tumor growth by inducing angiogenesis and by increasing HIF-1alpha and VEGF expression. This work provides a better understanding of the molecular mechanism of human cancer induced by the activation of PI3K signaling. [Description provided by NIOSH]
• Subjects:
  Carcinogens Neoplasms Occupational Health Safety
• Keywords:
  Cancer Physiology Tumor-inhibition Tumorigenesis Tumorigens Tumors
• ISSN:
  0021-9541
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  56-66
• Volume:
  209
• Issue:
  1
• NIOSHTIC Number:
  nn:20030949
• Citation:
  J Cell Physiol 2006 Oct; 209(1):56-66
• Contact Point Address:
  Bing-Hua Jiang, Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506- 9300
• Email:
  bhjiang@hsc.wvu.edu
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Cellular Physiology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3429977df198150f5964fd0f847e960297fac004128e9412f2aa16a4f6ff27a61805a5eeb0963bcbb6427221fd7675aec86f378683068ec124f9daae9ec5dad8
• Download URL:
  https://stacks.cdc.gov/view/cdc/191376/cdc_191376_DS1.pdf
• File Type:
  [PDF - 437.38 KB ]