Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias

• Published in: Nature (London) Vol. 329; no. 6136; p. 259
• Main Authors: Gisselbrecht, S, Fichelson, S, Sola, B, Bordereaux, D, Hampe, A, André, C, Galibert, F, Tambourin, P
• Format: Journal Article
• Language: English
• Published: England 17.09.1987
• Subjects: Animals; Base Sequence; Cell Transformation, Neoplastic; DNA, Neoplasm - genetics; DNA, Viral - genetics; Friend murine leukemia virus - genetics; Gene Expression Regulation; Growth Substances - genetics; Humans; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - microbiology; Mice; Nucleic Acid Hybridization; Proto-Oncogenes; RNA, Messenger - genetics
• ISSN: 0028-0836
• DOI: 10.1038/329259a0

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.