論文 - 詳細
| RRC ID | 54712 |
|---|---|
| 著者 | Gogola J, Hoffmann M, Ptak A. |
| タイトル | Persistent endocrine-disrupting chemicals found in human follicular fluid stimulate the proliferation of granulosa tumor spheroids via GPR30 and IGF1R but not via the classic estrogen receptors. |
| ジャーナル | Chemosphere |
| Abstract |
Epidemiological studies have found that women have detectable levels of organic pollutants such as hexachlorobenzene (HCB), 2,2-dichlorodiphenyldichloroethylene (p,p'-DDE), polychlorinated biphenyl 153 (PCB153), perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS) in their follicular fluid. Thus, these compounds may directly affect the function of granulosa cells within the ovary and may promote granulosa cell tumor (GCT) progression. Two human GCT cell lines, COV434 and KGN, have been used as in vitro model systems to represent juvenile (JGCT) and adult (AGCT) GCT subtypes, respectively. In this study, we found that basal expression of estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and insulin-like growth factor 1 receptor (IGF1R) was higher in the AGCT subtype than in the JGCT subtype. All of the compounds acted as mitogenic factors at low nanomolar concentrations in the JGCT and AGCT forms of GCT. Interestingly, PFOA, PFOS, and HCB stimulated cell proliferation through IGF1R, whereas p,p'-DDE acted through GPR30. Moreover, a mixture of the five compounds also significantly stimulated granulosa cell proliferation; however, the observed effect was lower than predicted. Interestingly, the proliferative effect of a mixture of these compounds was dependent on IGF1R and GPR30 but independent of the classic estrogen receptors. Taken together, our results demonstrate for the first time that mixtures of persistent organic pollutants present in follicular fluids may induce granulosa tumor progression through IGF1R and GPR30 by acting as mitogenic factors in granulosa cells. |
| 巻・号 | 217 |
| ページ | 100-110 |
| 公開日 | 2019-2-1 |
| DOI | 10.1016/j.chemosphere.2018.11.018 |
| PII | S0045-6535(18)32115-5 |
| PMID | 30414542 |
| MeSH | Adolescent Adult Cell Line, Tumor Cell Proliferation / drug effects Endocrine Disruptors / metabolism* Endocrine Disruptors / pharmacology Estrogen Receptor alpha / metabolism Estrogen Receptor beta / metabolism Female Follicular Fluid / chemistry* Granulosa Cell Tumor / etiology Granulosa Cell Tumor / pathology* Granulosa Cells / drug effects Granulosa Cells / pathology Humans Mitogens Ovarian Neoplasms Receptor, IGF Type 1 Receptors, Estrogen / analysis* Receptors, Estrogen / metabolism Receptors, Estrogen / physiology Receptors, G-Protein-Coupled / physiology* Receptors, Somatomedin / physiology* Young Adult |
| IF | 5.108 |
| 引用数 | 7 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Policy sources |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | KGN(RCB1154) |