title: Modulation of expression of 17-Hydroxylase/17,20 lyase (CYP17) and P450 aromatase (CYP19) by inhibition of MEK1 in a human ovarian granulosa-like tumor cell line.
abstract: The differential steroid production in the theca and granulosa cells in ovary are resulted from unique enzyme expression profiles. Among them, c-fos, a downstream target of mitogen and extracellular signal-regulated kinases (MEK/ERK) signaling, takes part in this compartment. In this study, we investigated the effect of c-fos on the steady-state levels of CYP17 and CYP19 in human ovarian granulosa-like tumor cell line (KGN) by inhibiting MEK/ERK pathway with PD98059. As a result, our finding demonstrated the distinct distribution patterns of CYP17 and CYP19 in KGN. Moreover, the MEK/ERK pathway functions to inhibit the production of CYP17, while enhance the production of CYP19 in granulosa cells, probably involving a c-fos-dependent mechanism. In conclusion, factors such as c-fos may play a crucial role in the down-regulation of CYP17 and up-regulation of CYP19 in granulosa cells, thereby suppressing androstenedione synthesis.
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Jin
authors.affiliation: b Divisions of Endocrinology , The Affiliated Drum Tower Hospital, Medical School, Nanjing University , Nanjing , China.
authors.forename: Shanmei
authors.initials: S
authors.lastname: Shen
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Xia
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zou
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University , Nanjing , China and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000735:Androstenedione / Q000378:metabolism; D001141:Aromatase / Q000378:metabolism*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006106:Granulosa Cell Tumor / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D016760:Proto-Oncogene Proteins c-fos; D000735:Androstenedione; D004958:Estradiol; D001141:Aromatase; C561410:CYP19A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: CYP17; CYP19; KGN; MEK/ERK; c-fos