Macrophage colony-stimulating factor is expressed by an ovarian carcinoma subline and stimulates the c-myc proto-oncogene.
A small, fast-growing and non-differentiated clone (N.1) derived from the heterogeneous human epithelial ovarian carcinoma cell line HOC-7 produces an autocrine/paracrine factor that is secreted into the cell culture supernatant. This factor is capable of enhancing mRNA levels of the proliferation-related oncogene c-myc in the more differentiated clone D3 and in normal human fibroblasts MRC.5, but also in N.1 cells themselves. Supernatants enriched for this paracrine/autocrine factor also confer a mitogenic stimulus as measured by [3H]thymidine incorporation. Trypsin can neutralise the stimulating activity of the secreted factor as well as monoclonal antibodies directed against macrophage colony-stimulating factor (M-CSF). We show that M-CSF and also M-CSF receptor are expressed in N.1 cells and that recombinant M-CSF induces c-myc transcript levels in N.1 cells. This investigation raises the possibility that M-CSF might be an autocrine growth factor in non-differentiated ovarian carcinomas. Inappropriate cytokine production could create a tumour-promoting microenvironment in this cancer type.
Krupitza
G
G
Department of Internal Medicine I, University of Vienna, Austria.
Fritsche
R
R
Dittrich
E
E
Harant
H
H
Huber
H
H
Grunt
T
T
Dittrich
C
C
D017209:Apoptosis; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D016259:Genes, myc; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D016186:Receptor, Macrophage Colony-Stimulating Factor