Endocrine Abstracts

The distinct roles of estrogen receptors (ERs) related with androgen receptors (ARs) have been proposed in prostate cancer, while the involvement of transforming growth factor-β (TGF-β) has been reported in prostate cancer progression. We examined that TGF-β signaling pathway is associated with ER signaling in LNCaP prostate cancer cells, which express ERα and ERβ, and ARs. We determined whether the exposure to phthalate may induce the prostate cancer progression by affecting molecular crosstalk between ER and TGF-β signaling pathways. Cell viability was measured in LNCaP cells by MTT assay following treatment with di-n-buthyl phthalate (DBP). RT-PCR and immunoblot assay were performed to examine the expression levels of cell cycle related genes and TGF-β signaling cascade. A mouse xenografted model of prostate cancer was generated, and immunohistochemical and BrdUrd assay were carried out to determine the effect of DBP in this mouse model. DBP was shown to promote LNCaP cell proliferation by upregulating gene expression of c-myc and cyclin D1 and by downregulating p21 expression. These regulations caused by DBP were reversed by ICI 182 780, indicating that DBP may affect the crosstalk between TGF-β and ER signals. In in vivo mouse model, tumor volume of mice exposed to DBP was increased. Number of cells in S phase of cell cycle was increased by DBP, while expression of p21 protein was reduced in the tissues of DBP-treated mice. These results indicate that DBP may induce the growth of prostate cancer by acting on crosstalk between TGF-β and ER signaling pathways.