SPI-1 transforming properties depend upon specifically activated forms of the EPOR.
Friend erythroleukemia induced in mice by the spleen focus forming virus (SFFV) is a multi-step process. The pre-leukemic phase of the disease results from the abnormal activation of the Erythropoietin (Epo) receptor by the gp55 env gene product of SFFV. Later in disease progression, the emergence of leukemic clones is associated with recurrent genetic events, in particular the activation of the expression of SPI-1, an ETS family transcriptional regulator. We show here that the expression of either SPI-1 or GP55 with the mouse EPOR in avian primary erythroblasts only marginally affects their normal Epo-induced terminal differentiation. In contrast, the co-expression of GP55 and SPI-1 resulted in inhibition of Epo-induced differentiation of EPOR-expressing erythroblasts, promoting instead their proliferation. Co-expression of SPI-1 and GP55 also inhibited the apoptotic cell death program normally induced in response to Epo withdrawal. This cooperation between SPI-1 and GP55 to induce primary erythroblast transformation suggests that progression of Friend erythroleukemia critically depends upon inter-dependent interactions between the molecular events specific of the early and late phase of the disease.
Pereira
R
R
CNRS UMR146 Institut Curie, Centre Universitaire, Bat. 110, 91405 Orsay, France.
Raingeaud
J
J
Pironin
M
M
Ghysdael
J
J
Quang
C T
CT
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D002645:Chickens; D004900:Erythroblasts / Q000166:cytology* / Q000378:metabolism / Q000821:virology; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000821:virology; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017467:Receptors, Erythropoietin / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D000099232:Proto-Oncogene Protein Spi-1
D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D000099232:Proto-Oncogene Protein Spi-1; C078780:glycoprotein gp55, Friend spleen focus-forming virus