The growth-regulatory role of B-cell-specific activator protein in NZB malignant B-1 cells.
The transcription factor B-cell-specific activator protein (BSAP) plays an important role in B-cell development. We explored the involvement of BSAP in the growth regulation of malignant B-1 cells derived from the NZB murine model of human chronic lymphocytic leukemia. BSAP protein was found in normal B-2 cells, elevated in normal B-1 cells, and highest in NZB malignant B-1 cells. When these malignant B-1 cells were treated with antisense oligonucleotides for BSAP, their growth was inhibited with a G2/M phase arrest. In contrast, B cell lines that did not appear to be of B-1 origin (IgG+/B220+/BSAPlow) were unaffected by treatment with antisense BSAP oligonucleotides. Centrifugal elutriation experiments showed that BSAP mRNA was expressed at the highest levels in the G2/M phases in malignant B-1 cells. Treatment with demecolcine (Colcemid), a known mitotic blocker, resulted in a decrease in the level of BSAP gene expression in malignant B-1 cells, further demonstrating links between BSAP expression and successful G2/M transition in the cell cycle. These data suggest a correlation between BSAP and the development of B-1 malignancy, perhaps through the regulation of cell-cycle progression.
Chong
S Y
SY
Department of Pathology, University of Medicine and Dentistry of New Jersey/New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Zhang
M
M
Lin
Y C
YC
Coffman
F
F
Garcia
Z
Z
Ponzio
N
N
Raveche
E S
ES
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000502:physiology*; D003703:Demecolcine / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D015321:Gene Rearrangement; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009687:Nuclear Proteins / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051757:PAX5 Transcription Factor; D014157:Transcription Factors
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D014157:Transcription Factors; D003703:Demecolcine