Document Detail

Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway.
MedLine Citation:
PMID:  16839745     Owner:  NLM     Status:  MEDLINE    
Ovarian cancer is the leading cause of death from gynecological malignancy for women. The amplification of the PI3K catalytic subunit (p110alpha) and the lost function of PTEN are frequently detected in ovarian cancer cells. PI3K plays an important role in tumorigenesis. To specifically inhibit PI3K activity in ovarian cancer cells, we constructed small interfering RNA (siRNA) against p110alpha. The expression of p110alpha siRNA significantly decreased cell migration, invasion, and proliferation compared to the siSCR control cells. The expression of p110alpha siRNA induced CDK inhibitor p27(KIP1) levels, and decreased levels of cyclin D1, CDK4, and phosphorylated retinoblastoma protein. PI3K transmits the mytogenic signal through AKT. AKT has three isoforms in the cells: AKT1, AKT2 and AKT3. We found that inhibition of AKT1 is sufficient to affect cell migration, invasion, and proliferation. Expression of AKT1 siRNA had a similar effect as p110alpha siRNA in the cells. We showed the roles of specific PI3K and AKT isoforms in the cells, which are important to understanding the mechanism of PI3K/AKT signaling in ovarian cancer cells. Both p110alpha and AKT1 siRNA-expressing cells decreased the activation of p70S6K1. Inhibition of p70S6K1 activity by its siRNA also decreased cell migration, invasion, and proliferation associated with the induction of p27(KIP1) levels, and with the inhibition of cell cycle-associated proteins including cyclin D1, CDK2, and phosphorylated retinoblastoma protein. This study demonstrates the important role of the PI3K/AKT/mTOR/p70S6K1 pathway in cell proliferation, migration, and invasion in ovarian cancer cells by using siRNA-mediated gene silencing as a reverse genetic method.
Qiao Meng; Chang Xia; Jing Fang; Yon Rojanasakul; Bing-Hua Jiang
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Publication Detail:
Type:  Journal Article     Date:  2006-06-02
Journal Detail:
Title:  Cellular signalling     Volume:  18     ISSN:  0898-6568     ISO Abbreviation:  Cell. Signal.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-10-31     Completed Date:  2007-02-05     Revised Date:  2012-06-19    
Medline Journal Info:
Nlm Unique ID:  8904683     Medline TA:  Cell Signal     Country:  England    
Other Details:
Languages:  eng     Pagination:  2262-71     Citation Subset:  IM    
Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506, USA.
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MeSH Terms
Catalytic Domain / genetics,  physiology
Cell Cycle / physiology
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Movement / physiology*
Cell Proliferation*
Cyclin-Dependent Kinase Inhibitor p27
Intracellular Signaling Peptides and Proteins / metabolism
Isoenzymes / genetics,  metabolism,  physiology
Neoplasm Invasiveness
Ovarian Neoplasms / metabolism,  pathology,  physiopathology
Phosphatidylinositol 3-Kinases / genetics,  metabolism*,  physiology
Proto-Oncogene Proteins c-akt / genetics,  metabolism*,  physiology
RNA Interference / physiology
RNA, Small Interfering / genetics
Ribosomal Protein S6 Kinases, 70-kDa / genetics,  metabolism*
Signal Transduction*
Reg. No./Substance:
0/CDKN1B protein, human; 0/Cell Cycle Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Isoenzymes; 0/RNA, Small Interfering; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC Proteins c-akt; EC Protein S6 Kinases, 70-kDa; EC protein S6 kinase, 70kD, polypeptide 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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