Role of PI3K/AKT/mTOR Signaling in G1 Cell Cycle Progression in Human Ovarian Cancer Cells

Details

• Personal Author:
  Flynn D ; Gao N ; Jiang BH ; Shi X
• Description:
  Ovarian cancer is one of the most common cancers among women. Recent studies demonstrated that the gene encoding the p110a catalytic subunit of phosphoinositide 3-kinase (PI3K) is frequently amplified in ovarian cancer cells. PI3K is involved in multiple cellular functions including proliferation, differentiation, anti-apoptosis, tumorigenesis, and angiogenesis. In this study, we demonstrate that the inhibition of PI3K activity by LY294002 inhibited ovarian cancer cell proliferation and induced the G1 cell cycle arrest. This effect was accompanied by the decreased expression of G1-associated proteins including cyclin D1, CDK4, CDC25A, and Rb phosphorylation at Ser780, Ser795, and Ser807/811. Whereas expression of CDK6 and b-actin was not affected by LY294002. Levels of cyclin kinase inhibitor, p161NK4 were induced by the PI3K inhibitor, while levels of p21CIP1/WAF1 were decreased in the same experiment. The inhibition of PI3K activity also inhibited the phosphorylation of AKT and p70S6K, but not MAPK. PI3K transmits a mitogenic signal through AKT, mTOR to p70S6K. The mTOR inhibitor rapamycin has similar inhibitory effects on G1 cell cycle progression and expression of cyclin D1, CDK4, CDC25A, and Rb phosphorylation. These results suggest that PI3K mediates G1 progression and cyclin expression through the activation of AKTI mTOR/p70S6K signaling pathway in the ovarian cancer cells. [Description provided by NIOSH]
• Subjects:
  Carcinogens Genetics Neoplasms Occupational Health Safety Urogenital Diseases Women
• Keywords:
  Cancer Carcinogenesis Cell-biology Cell-damage Cell-function Cellular-function Genetic-disorders Genetic-factors Reproductive-system-disorders Tumorigenesis Tumors

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• ISSN:
  0197-016X
• Publisher:
  American Association for Cancer Research
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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
• Volume:
  44
• NIOSHTIC Number:
  nn:20035519
• Citation:
  Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC. 2nd edition. Philadelphia, PA: American Association for Cancer Research, 2003 Jul; 44:400
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:111768981ba1670df76c390149c857d79f79ee1cebf3ef4826f60cfc920b816cd21cbce9df5e30aa43245aad5a2138aa581e6b15cdb465c69c97ffe86d58d4bd
• Download URL:
  https://stacks.cdc.gov/view/cdc/187351/cdc_187351_DS1.pdf
• File Type:
  [PDF - 258.77 KB ]