Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells

: Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wildlife and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and disrupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study. Methodology: In this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray. Results: Exposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes). Conclusion: We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.

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FOXA1: a transcription factor with parallel functions in development and cancer

Bioscience Reports ◽

10.1042/bsr20110046 ◽

2011 ◽

Vol 32 (2) ◽

pp. 113-130 ◽

Cited By ~ 99

Author(s):

Gina M. Bernardo ◽

Ruth A. Keri

Keyword(s):

Prostate Cancer ◽

Mammary Gland ◽

Hormone Receptors ◽

Developmental Pathways ◽

Hepatocyte Nuclear Factor ◽

Hormone Receptor Positive ◽

Forkhead Box ◽

Prostate Epithelial Cells ◽

Cancer Types ◽

Breast And Prostate Cancer

When aberrant, factors critical for organ morphogenesis are also commonly involved in disease progression. FOXA1 (forkhead box A1), also known as HNF3α (hepatocyte nuclear factor 3α), is required for postnatal survival due to its essential role in controlling pancreatic and renal function. In addition to regulating a variety of tissues during embryogenesis and early life, rescue experiments have revealed a specific role for FOXA1 in the postnatal development of the mammary gland and prostate. Activity of the nuclear hormone receptors ERα (oestrogen receptor α) and AR (androgen receptor) is also required for proper development of the mammary gland and prostate respectively. FOXA1 modulates ER and AR function in breast and prostate cancer cells, supporting the postulate that FOXA1 is involved in ER and AR signalling under normal conditions, and that some carcinogenic processes in these tissues stem from hormonally regulated developmental pathways gone awry. In addition to broadly reviewing the function of FOXA1 in various aspects of development and cancer, this review focuses on the interplay of FOXA1/ER and FOXA1/AR, in normal and cancerous mammary and prostate epithelial cells. Given the hormone dependency of both breast and prostate cancer, a thorough understanding of FOXA1's role in both cancer types is critical for battling hormone receptor-positive disease and acquired anti-hormone resistance.

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444: Identification of Genes Involved in Androgen Receptor Mutant-Induced Tumorigenesis of Human Prostate Epithelial Cells

The Journal of Urology ◽

10.1016/s0022-5347(18)32700-9 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 144-144

Author(s):

Xu-Bao Shi ◽

Lingru Xue ◽

Clifford G. Tepper ◽

Ralph W. deVere White

Keyword(s):

Androgen Receptor ◽

Epithelial Cells ◽

Human Prostate ◽

Prostate Epithelial Cells ◽

Receptor Mutant

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Faculty Opinions recommendation of Bisphenol A promotes human prostate stem-progenitor cell self-renewal and increases in vivo carcinogenesis in human prostate epithelium.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718238823.793489824 ◽

2014 ◽

Author(s):

Simon Hayward

Keyword(s):

Bisphenol A ◽

Progenitor Cell ◽

Human Prostate ◽

Self Renewal ◽

Prostate Epithelium

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Signal transduction of receptor-mediated antiproliferative action of melatonin on human prostate epithelial cells involves dual activation of Gαs and Gαq proteins

Journal of Pineal Research ◽

10.1111/j.1600-079x.2010.00795.x ◽

2010 ◽

Vol 49 (3) ◽

pp. 301-311 ◽

Cited By ~ 31

Author(s):

Stephen Y. W. Shiu ◽

Bo Pang ◽

Chun W. Tam ◽

Kwok-Ming Yao

Keyword(s):

Signal Transduction ◽

Epithelial Cells ◽

Human Prostate ◽

Antiproliferative Action ◽

Prostate Epithelial Cells ◽

Dual Activation

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CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers

Cancers ◽

10.3390/cancers13122872 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2872

Author(s):

Aaron R. Waddell ◽

Haojie Huang ◽

Daiqing Liao

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Tumor Growth ◽

Signaling Pathways ◽

Cell Cycle Progression ◽

Hormone Receptors ◽

Steroid Hormone Receptors ◽

Breast Cancers ◽

Creb Binding Protein ◽

Breast And Prostate Cancer

The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.

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Regulation of mRNA Translation by Hormone Receptors in Breast and Prostate Cancer

Cancers ◽

10.3390/cancers13133254 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3254

Author(s):

Jianling Xie ◽

Eric P. Kusnadi ◽

Luc Furic ◽

Luke A. Selth

Keyword(s):

Prostate Cancer ◽

Protein Synthesis ◽

Causes Of Death ◽

Hormone Receptors ◽

Mrna Translation ◽

Estrogen Receptor Α ◽

Growth And Survival ◽

Cancer Types ◽

Breast And Prostate Cancer ◽

Hormone Signalling

Breast and prostate cancer are the second and third leading causes of death amongst all cancer types, respectively. Pathogenesis of these malignancies is characterised by dysregulation of sex hormone signalling pathways, mediated by the estrogen receptor-α (ER) in breast cancer and androgen receptor (AR) in prostate cancer. ER and AR are transcription factors whose aberrant function drives oncogenic transcriptional programs to promote cancer growth and progression. While ER/AR are known to stimulate cell growth and survival by modulating gene transcription, emerging findings indicate that their effects in neoplasia are also mediated by dysregulation of protein synthesis (i.e., mRNA translation). This suggests that ER/AR can coordinately perturb both transcriptional and translational programs, resulting in the establishment of proteomes that promote malignancy. In this review, we will discuss relatively understudied aspects of ER and AR activity in regulating protein synthesis as well as the potential of targeting mRNA translation in breast and prostate cancer.

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