title: Cell Growth of BG-1 Ovarian Cancer Cells was Promoted by 4-Tert-octylphenol and 4-Nonylphenol via Downregulation of TGF-β Receptor 2 and Upregulation of c-myc.
abstract: Transforming growth factor β (TGF-β) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-β is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-β, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, ERα and ERβ, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/ERα and TGF-β pathway. Especially, based on the E2-mediated inhibition of TGF-β signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-β signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF- β receptor2 (TGF-β R2) in TGF-β signaling pathway. However, the expression level of TGF-β1 and TGF- β receptor1 (TGF-β R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-β signaling pathway. As a result of downregulation of TGF-β R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-β signaling via the downregulation of TGF-β R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-β signaling.
authors.affiliation: Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Chungbuk 361-763 Korea.
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Park
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Bo-Rim
authors.initials: BR
authors.lastname: Yi
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
keywords: Endocrine disrupting chemicals; Estrogen; NP; OP; Ovarian cancer cells; TGF-β1; c-myc