Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.
A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, was shown to potentiate long-term cultures of mouse bone marrow stromal cells in vitro and therefore constitutes a potential tool for immortalizing such cells. Moreover, when tested in an in vitro differentiation assay, stromal cells constitutively expressing c-fos favor the granulocyte differentiation of hematopoietic precursors. Interestingly, retroviruses expressing v-src and v-abl oncogenes, included as controls in our experiments, do not produce any detectable effects, whereas those expressing polyoma virus middle T antigen facilitate long-term growth in vitro of stromal cells that favor the macrophage differentiation pathway of bone marrow stem cells. Our observation supports the idea that constitutive expression of some oncogenes, including c-fos and polyoma virus middle T antigen, may influence cytokine production by bone marrow stromal cells.
Roux
P
P
UA CNRS 1191 Génétique Moléculaire, USTL, Montpellier, France.
Verrier
B
B
Klein
B
B
Niccolino
M
M
Marty
L
L
Alexandre
C
C
Piechaczyk
M
M
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods*; D005260:Female; D016762:Genes, fos / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics*; D011120:Polyomavirus; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D015183:Restriction Mapping; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D016760:Proto-Oncogene Proteins c-fos