In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein
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In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein. / Huss, R; Weissinger, E M; Lange, Claudia; Gatsios, P; Eissner, G; Kolb, H J; Diebold, J; Heinrich, P C; Graeve, L.
in: J PATHOL, Jahrgang 192, Nr. 3, 01.11.2000, S. 363-72.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein
AU - Huss, R
AU - Weissinger, E M
AU - Lange, Claudia
AU - Gatsios, P
AU - Eissner, G
AU - Kolb, H J
AU - Diebold, J
AU - Heinrich, P C
AU - Graeve, L
N1 - Copyright 2000 John Wiley & Sons, Ltd.
PY - 2000/11/1
Y1 - 2000/11/1
N2 - In an attempt to gain more insight into the events of leukaemic transformation, a cell line overexpressing MHC class II (DR) was generated by transfecting an early CD34-negative haematopoietic progenitor stem cell line with the appropriate constructs. The stable transfection with genes for DR antigens leads to cellular transformation. The DR(+) transformed cell clones express a tyrosine-phosphorylated DR heterodimer and show a significantly different morphology. DR(+) clones present the morphology of an immature myeloid neoplasia expressing alpha-naphthyl-acetate-esterase (ANAE), but neither myeloperoxidase nor CD34. While D064 cells predominately grow adherent as fibroblast-like cells, the DR(+) clones display a decrease in adherent growth. Although both cell lines express similar amounts of the interleukin-6 (IL-6) signal transducer gp130, the DR-transfected cells still show activation of STAT factors by IL-6, whereas D064 cells do not. Although the transformed clones present acceleration of cell-cycle transition and growth, the G(0)/G(1) progression inhibitor p27(kip-1) is up-regulated, while the expression of proteins involved in the S/G(2) phase transition, such as cyclin B and cdc2 (p34), is suppressed. Instead cyclin D3, one of the G(0)/G(1) progression factors, is up-regulated, as well as tyrosine-phosphorylated p62(dok), suggesting dysregulation of cell cycle-controlling proteins. In addition, DR(+) leukaemia-like cells also overexpress Bcl-2, while bax expression is suppressed, compared with the wild-type (wt) parental haematopoietic stem cell line.
AB - In an attempt to gain more insight into the events of leukaemic transformation, a cell line overexpressing MHC class II (DR) was generated by transfecting an early CD34-negative haematopoietic progenitor stem cell line with the appropriate constructs. The stable transfection with genes for DR antigens leads to cellular transformation. The DR(+) transformed cell clones express a tyrosine-phosphorylated DR heterodimer and show a significantly different morphology. DR(+) clones present the morphology of an immature myeloid neoplasia expressing alpha-naphthyl-acetate-esterase (ANAE), but neither myeloperoxidase nor CD34. While D064 cells predominately grow adherent as fibroblast-like cells, the DR(+) clones display a decrease in adherent growth. Although both cell lines express similar amounts of the interleukin-6 (IL-6) signal transducer gp130, the DR-transfected cells still show activation of STAT factors by IL-6, whereas D064 cells do not. Although the transformed clones present acceleration of cell-cycle transition and growth, the G(0)/G(1) progression inhibitor p27(kip-1) is up-regulated, while the expression of proteins involved in the S/G(2) phase transition, such as cyclin B and cdc2 (p34), is suppressed. Instead cyclin D3, one of the G(0)/G(1) progression factors, is up-regulated, as well as tyrosine-phosphorylated p62(dok), suggesting dysregulation of cell cycle-controlling proteins. In addition, DR(+) leukaemia-like cells also overexpress Bcl-2, while bax expression is suppressed, compared with the wild-type (wt) parental haematopoietic stem cell line.
KW - Acute Disease
KW - Apoptosis
KW - Blotting, Northern
KW - Blotting, Western
KW - Cell Communication
KW - Cell Cycle
KW - Cell Transformation, Neoplastic
KW - HLA-DR Antigens
KW - Humans
KW - In Situ Nick-End Labeling
KW - Interleukin-6
KW - Leukemia
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Tumor Cells, Cultured
KW - Up-Regulation
KW - ras GTPase-Activating Proteins
U2 - 10.1002/1096-9896(2000)9999:9999<::AID-PATH716>3.0.CO;2-N
DO - 10.1002/1096-9896(2000)9999:9999<::AID-PATH716>3.0.CO;2-N
M3 - SCORING: Journal article
C2 - 11054720
VL - 192
SP - 363
EP - 372
JO - J PATHOL
JF - J PATHOL
SN - 0022-3417
IS - 3
ER -