Biological activity of the receptor for macrophage colony-stimulating factor in the human endometrial cancer cell line, Ishikawa.
Previously we found that the Ishikawa endometrial cancer cell line expresses macrophage colony-stimulating factor (M-CSF) and c-fms transcripts and that its proliferation is enhanced by the addition of recombinant M-CSF. This suggested that Ishikawa cells are constitutively stimulated by M-CSF. In support of this we now show that Ishikawa cells secrete M-CSF and that known stimulators of M-CSF production increase the amount detected in Ishikawa cell conditioned medium. Using retroviral infections to introduce and express exogenous c-fms genes in Ishikawa cells we also demonstrate proliferation to be partially inhibited by a dominant negative, mutant c-fms gene, yet enhanced approximately 3-fold by a normal c-fms gene, under conditions in which the only source of M-CSF was that produced by the cells. The data provide evidence for the existence of an active M-CSF/receptor loop in these endometrial cancer cells and suggests the possibility of such activity in tumours of the endometrium and ovary that aberrantly express M-CSF and fms genes.
Takeda
S
S
Institute of Obstetrics and Gynaecology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Soutter
W P
WP
Dibb
N J
NJ
White
J O
JO
D001483:Base Sequence; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D016236:Genes, fms; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis; D008969:Molecular Sequence Data; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor