期刊
ONCOTARGET
卷 8, 期 70, 页码 115620-115631出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.23360
关键词
BPA; prostate cancer; cell cycle; AR; erk
资金
- AIRC (Associazione Italiana per la Ricerca sul Cancro)/FIRC Fellowship-Italy Guglielmina Lucatello e Gino Mazzega [17926]
- Italian Ministry of University and Scientific Research [2015B7M39T_003, 20152TE5PK_003]
- Regione Campania [5/2007]
- EU: BLUEPRINT [282510]
- Italian-Flag Project-EPIGEN
- AIRC [AIRC-17217]
Bisphenol A (BPA) belongs to the class of chemicals known as endocrine disruptors and has been also involved in the pathogenesis and progression of endocrine related cancer such as breast and prostate cancers. Here, we have investigated the effect of BPA in human prostate cancer LNCaP cells and in human non-transformed epithelial prostate EPN cells. Our data showed that BPA induces the down regulation of cyclin D1 expression and the upregulation of the cell cycle inhibitors p21 and p27, leading to cell cycle arrest. Interestingly, we found that the BPA anti-proliferative response depends on a strong and rapid activation of epidermal growth factor receptor (EGFR), which stimulates ERK-dependent pathway. This, in turn, induces expression of p53 and its phosphorylation on residue Ser15, which is responsible for cell cycle arrest. EGFR activation occurs upon a cross talk with androgen (AR) and estradiol receptor-beta (ER beta) which are known to bind BPA. Altogether, these findings show a novel signaling pathway in which EGFR activation plays a key role on BPA-induced cell cycle inhibition through a pathway involving AR and ER beta/EGFR complexes, ERK and p53. Our results provide new insights for understanding the molecular mechanisms in human prostate cancer. On the other, they could allow the development of new compounds that may be used to overcome human prostate cancer resistance to endocrine therapy in promising target therapeutic approaches.
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