The effects of S-phase kinase-associated protein 2 (SKP2) on cell cycle status, viability, and chemoresistance in A549 lung adenocarcinoma cells.
S-phase kinase-associated protein 2 (SKP2), a member of the F-box family of ubiquitin-protein ligase complexes, controls the stability of cell cycle-related proteins including p27Kip1. The authors examined how the expression level of SKP2 affects the expression level of cell cycle-related proteins, cell cycle status, viability, and chemoresistance in A549 lung adenocarcinoma cells. Overexpression of SKP2 reduced the expression of p27Kip1, cyclin E, and p21Cip1, increased S-phase cells, rescued A549 cells from apoptosis due to adenoviral infection, and also increased chemoresistance against camptothecin, cisplatin, and AG1478. Down-regulation of SKP2 did not affect cell cycle status, and reduced cell viability.
Ishii
Takeo
T
Department of Pulmonary Medicine, Yokohama City University Medical Center, Yokohama City, Japan.
Matsuse
Takeshi
T
Masuda
Michiaki
M
Teramoto
Shinji
S
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019927:Cyclin E / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011799:Quinazolines; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011799:Quinazolines; D044786:S-Phase Kinase-Associated Proteins; D020032:Tyrphostins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C101044:RTKI cpd; D002945:Cisplatin; D002166:Camptothecin