D Ripley1, X M Tang, C Ma, N Chegini. 1. Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
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. CONCLUSION: 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. Copyright 2001 Academic Press.
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 cancerpatients 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 humanendometrial 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. CONCLUSION: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. Copyright 2001 Academic Press.
Authors: Leonardo Martins; Camila Congentino Gallo; Tâmisa Seeko Bandeira Honda; Patrícia Terra Alves; Roberta Sessa Stilhano; Daniela Santoro Rosa; Timothy Jon Koh; Sang Won Han Journal: Stem Cell Res Ther Date: 2020-11-06 Impact factor: 6.832