Sherr C J
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
J Cell Physiol Suppl. 1987;Suppl 5:83-7. doi: 10.1002/jcp.1041330416.
The c-fms proto-oncogene encodes the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Although the tyrosine kinase activity of the CSF-1 receptor is stimulated by its ligand, the viral oncogene, v-fms, encodes a constitutive receptor kinase that can transform both fibroblasts and hematopoietic cells by a nonautocrine mechanism. Mutations in the c-fms gene as well as a critical alteration of the distal 3' coding sequences appear to be responsible for fully activating its latent transforming potential. The v-fms gene can convert CSF-1 or IL-3 dependent hematopoietic cell lines to factor independence and render them tumorigenic. Expression of the v-fms gene product does not transmodulate the normal receptors for CSF-1 or IL-3 and affects neither their affinity, number, nor potential to be independently down-regulated by their ligands or by phorbol esters. The ability of v-fms to transform hematopoietic target cells suggests that critical alterations in the c-fms proto-oncogene might similarly contribute to leukemia.
c-fms原癌基因编码单核吞噬细胞集落刺激因子（CSF-1）的受体。虽然CSF-1受体的酪氨酸激酶活性可被其配体激活，但病毒癌基因v-fms编码一种组成型受体激酶，它可通过非自分泌机制转化成纤维细胞和造血细胞。c-fms基因中的突变以及3'端编码序列远端的关键改变似乎是其潜在转化潜能完全激活的原因。v-fms基因可使依赖CSF-1或IL-3的造血细胞系不依赖这些因子，并使其具有致瘤性。v-fms基因产物的表达不会转调节CSF-1或IL-3的正常受体，对其亲和力、数量以及被其配体或佛波酯独立下调的潜能均无影响。v-fms转化造血靶细胞的能力表明，c-fms原癌基因中的关键改变可能同样会导致白血病。
