Intracisternal A-particle (IAP)-mediated leukemogenesis: levels and stability of IAP mRNA in FDC-P1 cells exposed to the conditions of an irradiated environment.
Following injection into sublethally irradiated DBA/2 or BALB/c mice, factor-dependent FDC-P1 cells undergo leukemic transformation due to oncogene activation by insertion of intracisternal A-particle (IAP) genetic elements. Similar events are observed in vitro during coculture of FDC-P1 cells with irradiated bone marrow stroma cells. To elucidate the mechanism of IAP transposition, we studied the level of IAP expression under the growth conditions preceding cell transformation. In vitro experiments showed that the type of growth factor, FDC-P1 cell density, costimulation with steroid hormones or abrupt growth factor withdrawal had no effect on IAP mRNA levels (major transcripts of 7.4, 4.0 and 1.9 kb). By contrast, stimulation with suboptimal concentrations of GM-CSF or IL-3 induced a mean 2. 5-fold increase in the intensity of the 7.4 kb band, and induction of macrophage differentiation with retinoic acid resulted in an increased stability of the 4.0 kb band. Although suboptimal growth stimulation and incipient macrophage differentiation have previously been shown to occur in the process of FDC-P1 cell transformation, an increase in IAP expression could not convincingly be demonstrated in FDC-P1 cell populations isolated from irradiated BALB/c mice or stroma cell cocultures. Further experiments are required to define the role of suboptimal growth stimulation and/or macrophage differentiation in this transformation model.
Blumenstein
M
M
Abteilung für Onkologie und Hämatologie, Medizinische Klinik, Universitätskrankenhaus Eppendorf, Hamburg, Germany.
Tessmer
U
U
Hossfeld
D K
DK
Dührsen
U
U
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007426:Genes, Intracisternal A-Particle / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014212:Tretinoin / Q000494:pharmacology; D014916:Whole-Body Irradiation
D000970:Antineoplastic Agents; D012739:Gonadal Steroid Hormones; D007377:Interleukin-3; D012333:RNA, Messenger; D014212:Tretinoin; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor