title: Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias.
abstract: Retroviruses lacking oncogenes can induce tumours in animals, and the tumour cells are frequently found to contain proviral DNA inserted next to a proto-oncogene, which is thus placed under the regulatory control of the retroviral long terminal repeat (LTR). This altered regulation leads to overexpression of the proto-oncogene, which presumably contributes to the growth properties of the tumour cells. fim-2 has been described as a retroviral integration site frequently and specifically involved in murine myeloblastic leukaemias induced in vivo or in vitro by the replication-competent Friend murine leukaemia virus (F-MuLV). Here we report that fim-2 spans the 5'-end of the murine proto-oncogene c-fms, known to code for a transmembrane glycoprotein with tyrosine kinase activity probably identical to the receptor of the haemopoietic growth factor, monocyte-macrophage colony-stimulating factor (M-CSF or CSF-1). Proviral integration in the fim-2 region results in a high expression of a normal sized c-fms messenger RNA. We also observe that some tumours have lost the fim-2/c-fms germ line allele. These results provide the first evidence for the presumed involvement of c-fms in myelomonocytic leukaemias.
mesh_terms: D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005622:Friend murine leukemia virus / Q000235:genetics*; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000382:microbiology; D051379:Mice; D009693:Nucleic Acid Hybridization; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral; D006133:Growth Substances; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger