+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Combined Loss of EAF2 and p53 Induces Prostate Carcinogenesis in Male Mice



Combined Loss of EAF2 and p53 Induces Prostate Carcinogenesis in Male Mice



Endocrinology 158(12): 4189-4205



Mutations in the p53 tumor suppressor are frequent in patients with castration-resistant prostate cancer but less so in patients with localized disease, and patients who have Li-Fraumeni with germline p53 mutations do not have an increased incidence of prostate cancer, suggesting that additional molecular and/or genetic changes are required for p53 to promote prostate carcinogenesis. ELL-associated factor 2 (EAF2) is a tumor suppressor that is frequently downregulated in advanced prostate cancer. Previous studies have suggested that p53 binds to EAF2, providing a potential mechanism for their functional interactions. In this study, we tested whether p53 and EAF2 could functionally interact in prostate cancer cells and whether concurrent inactivation of p53 and EAF2 could promote prostate carcinogenesis in a murine knockout model. Endogenous p53 coprecipitated with EAF2 in prostate cancer cells, and deletion mutagenesis indicated that this interaction was mediated through the C terminus of EAF2 and the DNA binding domain of p53. Concurrent knockdown of p53 and EAF2 induced an increase in proliferation and migration in cultured prostate cancer cells, and conventional p53 and EAF2 knockout mice developed prostate cancer. In human prostate cancer specimens, concurrent p53 nuclear staining and EAF2 downregulation was associated with high Gleason score. These findings suggest that EAF2 and p53 functionally interact in prostate tumor suppression and that simultaneous inactivation of EAF2 and p53 can drive prostate carcinogenesis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 059520455

Download citation: RISBibTeXText

PMID: 29029019

DOI: 10.1210/en.2017-00409


Related references

Concurrent EAF2 and ELL2 loss phenocopies individual EAF2 or ELL2 loss in prostate cancer cells and murine prostate. American Journal of Clinical and Experimental Urology 6(6): 234-244, 2018

EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate. Angiogenesis 14(3): 331-343, 2011

Chemoprevention of prostate carcinogenesis and inhibitory effects on progression of prostate carcinogenesis in SCID mice by dietary curcumin isolated from curcumin longa linn. European Urology Suppl.s 3(2): 91, 2004

Continuous PTH in Male Mice Causes Bone Loss Because It Induces Serum Amyloid A. Endocrinology 159(7): 2759-2776, 2018

Beta-Carotene fails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Sencar mice. Nutrition and Cancer 37(1): 82-88, 2000

Generation of transgeneic mice that specifically express PSM or PSM in the prostate for the study of prostate carcinogenesis and prostate cancer therapy. Proceedings of the American Association for Cancer Research Annual Meeting 40: 654, 1999

Maternal Low-Protein Diet Impairs Prostate Growth in Young Rat Offspring and Induces Prostate Carcinogenesis With Aging. Journals of Gerontology. Series A Biological Sciences and Medical Sciences 74(6): 751-759, 2019

Loss of survivin in the prostate epithelium impedes carcinogenesis in a mouse model of prostate adenocarcinoma. Plos one 8(7): E69484, 2013

CHC1-L, a candidate gene for prostate carcinogenesis at 13q14.2, is frequently affected by loss of heterozygosity and underexpressed in human prostate cancer. International Journal of Cancer 99(5): 689-696, 2002

Combined loss of the GATA4 and GATA6 transcription factors in male mice disrupts testicular development and confers adrenal-like function in the testes. Endocrinology 156(5): 1873-1886, 2015

EAF2 and p53 Co-Regulate STAT3 Activation in Prostate Cancer. Neoplasia 20(4): 351-363, 2018

Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: comparison with RANKL-overexpressing transgenic male mice. Endocrinology 154(2): 773-782, 2013

The Y chromosome from autoimmune BXSB/MpJ mice induces a lupus-like syndrome in (NZW x C57BL/6)F1 male mice, but not in C57BL/6 male mice. European Journal of Immunology 18(6): 911-915, 1988

Regulation of ELL2 stability and polyubiquitination by EAF2 in prostate cancer cells. Prostate 78(15): 1201-1212, 2018

Exposure to TNF‑α combined with TGF‑β induces carcinogenesis in vitro via NF-κB/Twist axis. Oncology Reports 37(3): 1873-1882, 2017