Retroviral infection can abrogate the factor-dependency of hematopoietic cells by autocrine and non-autocrine mechanisms depending on the presence of a functional viral oncogene
McCubrey, J.A.; Smith, S.R.; Algate, P.A.; DeVente, J.E.; White, M.K.; Steelman, L.S.
Oncogene 8(11): 2905-2915
1993
ISSN/ISBN: 0950-9232 PMID: 8414494 Document Number: 418521
The mechanisms responsible for abrogation of the growth factor-dependency of a hematopoietic cell line were investigated. FDC-P1 cells were infected with retroviral constructs containing the neo gene and either a wild-type or a temperature-sensitive v-src oncogene. v-src-wt abrogated the factor-dependency of these cells since each G418-r colony gave rise to factor-independent cells and no autocrine growth factor activity was detected. Moreover, the vast majority ( lt 99%) of cells infected with the v-src-ts mutant gave rise to conditional factor-independent cells. Therefore a functional v-src gene product was required for growth factor-independence which occurred by a non-autocrine mechanism. A minority of factor-independent cells which arose after v-src-ts infection, grew at the non-permissive temperature and one-half secreted granulocyte/macrophage-colony stimulating factor (GM-CSF) which supports the growth of the parental cells. Since the v-src-ts viral stock contained a helper virus, Murine Leukemia Virus (MuLV), the ability of this virus to relieve factor-dependency was examined. A low frequency of factor-independent transformants was recovered after MuLV infection and one-half secreted GM-CSF. Therefore, retroviruses such as MuLV which lack an oncogene, can transform cells by stimulating autocrine growth factor secretion. Subsequent experiments performed with helper-free v-src preparations indicated that they could abrogate factor-dependency directly by a non-autocrine mechanism. These results demonstrate that a hematopoietic cell line can be transformed by two different mechanisms after retroviral infection and may be relevant for understanding hematopoietic cell transformation after persistent viral infection.