Concurrent EAF2 and ELL2 loss phenocopies individual EAF2 or ELL2 loss in prostate cancer cells and murine prostate.

Autor:	Zhong M; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Pascal LE; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Cheng E; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Masoodi KZ; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.; Transcriptomics Lab, Division of Plant Biotechnology SKUAST-K, Shalimar, Srinagar, J&K, India., Chen W; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Green A; Department of Pathology, Pitt Biospecimen Core, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Cross BW; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Parrinello E; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Rigatti LH; Division of Laboratory Animal Resources, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA., Wang Z; University of Pittsburgh Cancer Institute, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.; Department of Urology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	American journal of clinical and experimental urology [Am J Clin Exp Urol] 2018 Dec 20; Vol. 6 (6), pp. 234-244. Date of Electronic Publication: 2018 Dec 20 (Print Publication: 2018).
Abstrakt:	Elongation factor for RNA polymerase II 2 (ELL2) and ELL-associated factor 2 (EAF2) are two functionally related androgen responsive gene-encoded proteins with prostate tumor suppressor characteristics. EAF2 and ELL2 have both been shown to be down-regulated in advanced prostate cancer, and mice with either Eaf2 or Ell2 deficiency developed murine prostatic intraepithelial neoplasia (mPIN), increased cellular proliferation and increased vascularity. Functional studies have revealed that EAF2 and ELL2 can bind to each other and have similar roles in regulating cell proliferation, angiogenesis and prostate homeostasis. Here, cell line experiments showed that knockdown of EAF2 or ELL2 induced an increase in proliferation and migration in C4-2 and 22Rv1 prostate cancer cells. Concurrent knockdown of EAF2 and ELL2 increased proliferation and migration similarly to the loss of EAF2 or ELL2 alone. Mice with homozygous deletion of Ell2 or heterozygous deletion of Eaf2 developed mPIN lesions characterized by increased epithelial proliferation, intraductal microvessel density, and infiltrating intraductal CD3-positive T-cells compared to wild-type controls. Mice with combined heterozygous deletion of Eaf2 and Ell2 developed mPIN lesions that were similar to those observed in mice with deficiency in Eaf2 or Ell2 alone. These results suggest that EAF2 and ELL2 have similar functions and are likely to require each other in their regulation of prostate epithelial cell proliferation and migration in prostate cancer cells as well as their tumor suppressive properties in the murine prostate. Competing Interests: None.
Databáze:	MEDLINE
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