Bisphenol A induces cell cycle arrest in primary and prostate cancer cells through EGFR/ERK/p53 signaling pathway activation.
Bisphenol A induces cell cycle arrest in primary and prostate cancer cells through EGFR/ERK/p53 signaling pathway activation.
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Bisphenol A通过EGFR/ERK/p53信号通路激活诱导原发性和前列腺癌细胞中的细胞周期停滞。
DOI：
10.18632/oncotarget.23360
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发表时间：
2017-12-29
期刊：
影响因子：
--
通讯作者：
Castoria G
中科院分区：
文献类型：
--
作者：
Bilancio A;Bontempo P;Di Donato M;Conte M;Giovannelli P;Altucci L;Migliaccio A;Castoria G
双酚A （BPA）属于被称为内分泌干扰物的化学物质，也参与了内分泌相关癌症（如乳腺癌和前列腺癌）的发病和进展。在这里，我们研究了BPA对人前列腺癌LNCaP细胞和人非转化上皮前列腺EPN细胞的影响。我们的数据表明，BPA诱导细胞周期蛋白D1表达下调，细胞周期抑制剂p21和p27表达上调，导致细胞周期阻滞。有趣的是，我们发现BPA的抗增殖反应依赖于表皮生长因子受体（EGFR）的强烈和快速激活，这刺激了erk依赖通路。这进而诱导p53的表达及其在残基Ser15上的磷酸化，这是细胞周期阻滞的原因。EGFR激活发生在雄激素（AR）和雌二醇受体-β (ERβ)的串扰中，已知雄激素和雌二醇受体-β与BPA结合。总之，这些发现表明了一种新的信号通路，其中EGFR激活在bpa诱导的细胞周期抑制中起关键作用，该通路涉及AR和ERβ/EGFR复合物、ERK和p53。我们的研究结果为理解人类前列腺癌的分子机制提供了新的见解。另一方面，它们可以开发出新的化合物，用于克服人类前列腺癌对内分泌治疗的耐药性，成为有希望的靶向治疗方法。
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-β (ERβ) 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 ERβ/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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影响因子：
12.4
作者：
通讯作者：
--
DOI：
10.1016/j.reprotox.2016.07.020
发表时间：
2017-03
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Rubin BS;Paranjpe M;DaFonte T;Schaeberle C;Soto AM;Obin M;Greenberg AS
通讯作者：
Greenberg AS
影响因子：
7.4
作者：
Bontempo P;Mita L;Doto A;Miceli M;Nebbioso A;Lepore I;Franci G;Menafra R;Carafa V;Conte M;De Bellis F;Manzo F;Di Cerbo V;Benedetti R;D'Amato L;Marino M;Bolli A;Del Pozzo G;Diano N;Portaccio M;Mita GD;Vietri MT;Cioffi M;Nola E;Dell'aversana C;Sica V;Molinari AM;Altucci L
通讯作者：
Altucci L
影响因子：
2.6
作者：
Kovanecz, I.;Gelfand, R.;Masouminia, M.;Gharib, S.;Segura, D.;Vernet, D.;Rajfer, J.;Li, D. K.;Kannan, K.;Gonzalez-Cadavid, N. F.
通讯作者：
Gonzalez-Cadavid, N. F.
DOI：
10.1016/j.jsbmb.2011.05.002
发表时间：
2011-10-01
影响因子：
4.1
作者：
Rubin, Beverly S.
通讯作者：
Rubin, Beverly S.