title: 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.
abstract: 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-srcwt abrogated the factor-dependency of these cells since each G418r colony gave rise to factor-independent cells and no autocrine growth factor activity was detected. Moreover, the vast majority (< 99%) of cells infected with the v-srcts 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-srcts 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-srcts 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.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
authors.forename: J A
authors.initials: JA
authors.lastname: McCubrey
authors.forename: S R
authors.initials: SR
authors.lastname: Smith
authors.forename: P A
authors.initials: PA
authors.lastname: Algate
authors.forename: J E
authors.initials: JE
authors.lastname: DeVente
authors.forename: M K
authors.initials: MK
authors.lastname: White
authors.forename: L S
authors.initials: LS
authors.lastname: Steelman
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis; D016391:Genes, src; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000382:microbiology; D051379:Mice; D015688:Oncogene Protein pp60(v-src) / Q000502:physiology; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D012190:Retroviridae / Q000235:genetics* / Q000502:physiology; D013696:Temperature
chemical_list: D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D015688:Oncogene Protein pp60(v-src)