Proteomic analysis of interleukin 6-induced differentiation in mouse myeloid leukemia cells.
Cytokine-induced differentiation of myeloid leukemia cells has important therapeutic implications, but the mechanism remains to be clarified. M1 cell, a mouse acute myeloid leukemia cell line, which underwent growth inhibition, terminal differentiation and apoptosis in response to IL-6, was selected as an experimental model to study on the molecular mechanisms of myeloid cell differentiation on a proteome-wide scale. Cell differentiation was evaluated by cell morphology and CD11b expression. With two-dimensional (2D) gel analyses, 17 protein spots showed obvious changes in quantity during the process of differentiation were found. With matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF-MS) or/and nano-electrospray ionization MS/MS (ESI-MS/MS) analysis, 15 protein spots were identified. The mRNA levels of these 15 proteins during differentiation were also examined using a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Except two proteins, the mRNA levels demonstrated similar expression patterns to what the proteomic analysis revealed. The identified proteins were known to be involved in different cellular functions, including protein synthesis, transcription, signal transduction, cell cycle control, cell rescue and defense, cellular organization, and metabolism. Notably, seven proteins were not described before to be involved in differentiation. Our data provide novel information for a better understanding of the mechanisms by which terminal differentiation of acute myeloid leukemia cells induced by IL-6.
Xia
Qing
Q
Department of Molecular Immunology, Beijing Institute of Basic Medical Science, TaiPing Road 27, Beijing 100850, PR China.
Wang
Hong-Xia
HX
Wang
Jie
J
Zhang
Ji-Yan
JY
Liu
Bing-Ying
BY
Li
Ai-Ling
AL
Lv
Ming
M
Hu
Mei-Ru
MR
Yu
Ming
M
Feng
Jian-Nan
JN
Yang
Song-Cheng
SC
Zhang
Xue-Min
XM
Shen
Bei-Fen
BF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D055313:Cystatin B; D015891:Cystatins / Q000096:biosynthesis; D015180:Electrophoresis, Gel, Two-Dimensional; D005634:Fructose-Bisphosphate Aldolase / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D010544:Peroxidases / Q000096:biosynthesis; D054464:Peroxiredoxins; D040901:Proteomics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D039481:CD11b Antigen; C524992:Cstb protein, mouse; D015891:Cystatins; D015850:Interleukin-6; D008565:Membrane Proteins; D011994:Recombinant Proteins; D055313:Cystatin B; D010544:Peroxidases; D054464:Peroxiredoxins; D005634:Fructose-Bisphosphate Aldolase