title: The biological effects of macrophage-colony-stimulating factor induced by progestin on growth and differentiation of endometrial adenocarcinoma cells.
abstract: Progestins have biological effects of regression and differentiation on human endometrial adenocarcinoma. We investigated the effects of progestin on the induction of macrophage-colony-stimulating factor (M-CSF) and its receptor messenger RNAs in the human endometrial adenocarcinoma cell line Ishikawa which has receptors for both estrogen and progesterone. Poly(A)+RNA extracted from Ishikawa cells cultured with or without synthetic progestin R5020 was subjected to Northern blot hybridization using M-CSF and c-fms cDNA probes. The expression of M-CSF mRNA in Ishikawa cells increased about 2.3 times following treatment with R5020 at 10(-7) M. Induction of M-CSF mRNA by R5020 was antagonized by anti-progestin RU486 in a dose-dependent manner. However, c-fms mRNA, coding the M-CSF receptor, was expressed constitutively in Ishikawa cells and its expression was not affected by hormonal treatment. We further examined the biological effects of M-CSF on endometrial cancer cells. Colony formation of Ishikawa cells in soft agar, which represents anchorage-independent cell growth, was inhibited by M-CSF treatment. On the other hand, accumulation of glycogen granules in cytoplasm detected by periodicacid-Schiff staining was observed in Ishikawa cells treated with M-CSF. These results indicate that M-CSF, whose gene expression was enhanced by progestin, suppressed growth and induced differentiation of endometrial adenocarcinoma cells. These effects of M-CSF on endometrial cancer cells are similar to those of progestins, so the effects of progestins on these cells are, at least in part, probably mediated by M-CSF in an autocrine or paracrine manner.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: C
authors.initials: C
authors.lastname: Azuma
authors.forename: F
authors.initials: F
authors.lastname: Saji
authors.forename: Y
authors.initials: Y
authors.lastname: Tokugawa
authors.forename: M
authors.initials: M
authors.lastname: Takemura
authors.forename: M
authors.initials: M
authors.lastname: Miki
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: O
authors.initials: O
authors.lastname: Tanizawa
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D016236:Genes, fms; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D015735:Mifepristone / Q000494:pharmacology; D011372:Progestins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000473:pathology*
chemical_list: D011372:Progestins; D012333:RNA, Messenger; D015735:Mifepristone; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor