Growth, differentiation, and malignant transformation of pre-B cells mediated by inducible activation of v-Abl oncogene.
The nonreceptor tyrosine kinase, encoded by the v-Abl oncogene of Abelson murine leukemia virus induces transformation of progenitor B cells. The v-Abl oncogene promotes cell cycle progression and inhibits pre-B cell differentiation. The temperature-sensitive form of Abelson murine leukemia virus offers a reversible model to study the role of v-Abl in regulating growth and differentiation. Inactivation of v-Abl elevates p27 and Foxo3a levels and activates NF-kappaB/Rel, which leads to G1 arrest and induction of Ig L chain gene rearrangement, respectively. In turn, v-Abl reactivation reduces p27 and Foxo3a levels, thus permitting G1-arrested cells to reenter the cell cycle. However, the cell lines derived from SCID mice that are defective in the catalytic subunit of DNA-dependent protein kinase retain elevated levels of p27 and Foxo3a proteins despite reactivation of v-Abl. Consequently, these cells are locked in the G1 phase for an extended period of time. The few cells that manage to bypass the G1 arrest become tumorigenic and fail to undergo pre-B cell differentiation induced by v-Abl inactivation. Deregulation of p27, Foxo3a, c-myc, and NF-kappaB/Rel was found to be associated with the malignant transformation of SCID temperature-sensitive form of Abelson murine leukemia virus pre-B cells.
Jacobsen
Elizabeth A
EA
Molecular and Cellular Biology Program, School of Life Sciences, The Biodesign Institute at Arizona State University, Tempe, AZ 85287, USA.
Ananieva
Olga
O
Brown
Matthew L
ML
Chang
Yung
Y
D000011:Abelson murine leukemia virus / Q000502:physiology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D016313:Genes, abl / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism; D013696:Temperature
D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel