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Farnesoid X Receptor ligand down‐regulates aromatase expression in Leydig tumor cells.
Author(s) -
Andò Sebastiano,
Malivindi Rocco,
Rizza Pietro,
Go Guowei,
Catalano Stefania
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.599
Subject(s) - aromatase , farnesoid x receptor , medicine , endocrinology , biology , cancer research , nuclear receptor , estrogen receptor , progesterone receptor , chemistry , cancer , transcription factor , breast cancer , biochemistry , gene
Males between 15 and 34 years of age are frequently affected by testicular solid tumors, 95% of which originate from germinal cells whereas Leydig cell tumors are the most common tumors of gonadal stroma. We evidenced a strong aromatase expression in human Leydig tumor tissues addressing how an enhanced local estrogen production may contribute to tumor growth and progression. Farnesoid X receptor (FXR), has been characterized as a bile acid receptor, expressed in several non‐enterohepatic tissues including testis. Recently, it has been demonstrated that FXR activation represses aromatase expression in breast cancer cells. Our results evidenced, that in rat Leydig tumor cells (R2C), specific FXR ligand, chenodeoxycholic acid (CDCA), enhanced FXR levels, decreased aromatase expression in terms of protein content, mRNA and aromatase enzymatic activity and concomitantly inhibits cell proliferation. Transient transfection experiment, using vector containing rat aromatase promoter PII, evidenced that CDCA reduced basal aromatase promoter activity. Even though its remains to be elucidated the molecular mechanism trough which FXR/CDCA inhibits aromatase gene expression in the testis, our present findings address how FXR ligand may be perspectively considered potential pharmacological tools to be implemed in the novel strategies for testicular tumor treatment.