Role of the phosphatidylinositol 3'-kinase-Akt signal pathway in the proliferation of human pancreatic ductal carcinoma cell lines.
: Phosphatidylinositol 3'-kinase (PI3K) and Akt mediate survival signals and allow the cells to escape apoptosis in various human cancers. We postulated that LY294002, a PI3K inhibitor, might inactivate Akt, consequently inhibiting cell proliferation in 3 human pancreatic ductal carcinoma cell lines, PSN-1, PANC-1, and KP-4. LY294002 (50 micromol/L) caused a decrease in phosphorylated Akt and inhibition of cell proliferation in a time-dependent manner, but there was no obvious induction of apoptosis. Flow cytometric analysis revealed that pancreatic cancer cells treated with 50 micromol/L LY294002 underwent G1 arrest, which was associated with dephosphorylation of the ppRB protein, a decrease in the protein expression of cyclin D and E, and their activating partners Cdk2, 4, and 6 with simultaneous accumulation of P27/Kip1. Our data indicate that P27/Kip1 accumulation by Akt inactivation could induce cell cycle arrest in the G1 phase and suggest that the PI3K-Akt pathway plays an important role in cell proliferation in human pancreatic ductal carcinoma cells.
Takeda
Ami
A
Division of Organ Pathology, Department of Microbiology and Pathology, Graduate School of Medicine, Tottori University, Yonago, Japan.
Osaki
Mitsuhiko
M
Adachi
Keiko
K
Honjo
Soichiro
S
Ito
Hisao
H
D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects
D018797:Cell Cycle Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494918:AKT1 protein, human