title: The expression and action of granulocyte macrophage-colony stimulating factor and its interaction with TGF-beta in endometrial carcinoma.
abstract: OBJECTIVE
  Previous studies have demonstrated that normal human endometrium expresses granulocyte macrophage-colony stimulating factor (GM-CSF) and GM-CSF receptors. Because GM-CSF is administer to cancer patients following chemotherapy, GM-CSF may directly or through interaction with ovarian steroids and other cytokines alter the behavior of endometrial cancer. The aim of this study was to determine the expression of GM-CSF and receptors in endometrial carcinoma and its direct effect and interaction with transforming growth factor beta (TGF-beta) on Ishikawa cells, a human endometrial carcinoma cell line.
  
  
  METHODS
  GM-CSF, GM-CSF receptors, TGF-beta1, and TGF-beta type II receptor expression were evaluated using quantitative reverse transcription polymerase chain reaction (Q-RT-PCR). The effect of GM-CSF on DNA synthesis, cell proliferation, expression of GM-CSF, TGF-beta1, and TGF-beta receptor, and their regulation by ovarian steroids was determined by the rate of [(3)H]thymidine incorporation, MTT assay, Q-RT-PCR, and ELISA, respectively.
  
  
  RESULTS
  Endometrial carcinomas express significantly higher GM-CSF and GM-CSF alpha and beta receptor mRNA compared with normal postmenopausal endometrium. GM-CSF at various doses had no significant effect on the rate of [(3)H]thymidine incorporation or proliferation of Ishikawa cells, whereas TGF-beta1 inhibited [(3)H]thymidine incorporation. GM-CSF and TGF-beta1 regulate their own expression and the expression of TGF-beta type II receptor, which were both upregulated by 17beta-estradiol and medroxyprogesterone acetate treatment and reversed following cotreatment with their respective receptor antagonists.
  
  
  CONCLUSIONS
  Endometrial carcinoma expresses an elevated level of GM-CSF and GM-CSF receptors. GM-CSF is not a mitogen for the endometrial cancer cell line; however, either alone or through interaction with TGF-beta1, it regulates its own expression and the expression of TGF-beta1 and TGF-beta type II receptor which inhabits endometrial cancer cells. This interaction may represent a regulatory feedback mechanism that could serve to suppress endometrial carcinoma growth.
authors.affiliation: Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ripley
authors.forename: X M
authors.initials: XM
authors.lastname: Tang
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: N
authors.initials: N
authors.lastname: Chegini
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D018931:Antineoplastic Agents, Hormonal; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004958:Estradiol; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017258:Medroxyprogesterone Acetate; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II