論文 - 詳細
RRC ID | 1319 |
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著者 | Takeda A, Osaki M, Adachi K, Honjo S, Ito H. |
タイトル | Role of the phosphatidylinositol 3'-kinase-Akt signal pathway in the proliferation of human pancreatic ductal carcinoma cell lines. |
ジャーナル | Pancreas |
Abstract |
: 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. |
巻・号 | 28(3) |
ページ | 353-8 |
公開日 | 2004-4-1 |
DOI | 10.1097/00006676-200404000-00026 |
PII | 00006676-200404000-00026 |
PMID | 15084985 |
MeSH | Apoptosis Carcinoma, Pancreatic Ductal / enzymology* Carcinoma, Pancreatic Ductal / metabolism Carcinoma, Pancreatic Ductal / pathology Cell Cycle / drug effects Cell Cycle Proteins / metabolism Cell Division / drug effects Cell Line, Tumor Chromones / pharmacology Down-Regulation Enzyme Inhibitors / pharmacology Humans Morpholines / pharmacology Pancreatic Neoplasms / enzymology* Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Phosphatidylinositol 3-Kinases / metabolism Phosphatidylinositol 3-Kinases / physiology* Phosphoinositide-3 Kinase Inhibitors Protein Serine-Threonine Kinases* Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins / physiology* Proto-Oncogene Proteins c-akt Signal Transduction* / drug effects |
IF | 2.92 |
引用数 | 42 |
WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
リソース情報 | |
ヒト・動物細胞 | KP4(RCB1005) |