Gene Expression Profiling Reveals Regulation of ERK Phosphorylation by Androgen-Induced Tumor Suppressor U19/EAF2 in the Mouse Prostate

Overview

Journal Cancer Microenviron

Publisher Springer

Specialty Oncology

Date 2013 Feb 27

PMID 23440596

Citations 9

Authors

Fei Su

Bruna R S Correa

Jianhua Luo

Ricardo Z N Vencio

Laura E Pascal

Zhou Wang

Affiliations

Soon will be listed here.

Abstract

U19/EAF2 is regulated by androgens in the prostate and capable of regulating transcriptional elongation of RNA Pol II via interaction with the ELL family proteins. Inactivation of U19/EAF2 induces tumorigenesis in multiple organs; however the mechanism of U19/EAF2 tumor suppression remains unclear. To elucidate potential mechanisms of U19/EAF2 action, we performed cDNA microarray analysis and identified 164 mRNA transcripts regulated by U19/EAF2 in the mouse ventral prostate. Bioinformatics analysis indicated that U19/EAF2 knockout activates the RAS-BRAF-ERK signaling pathway, which is known to play important roles in carcinogenesis. qPCR verified increased expression of BRAF mRNA, and immunostaining and Western blot analysis demonstrated increased expression of p-ERK at the protein level suggested U19/EAF2 knockout activates this important pathway. These findings indicate that loss of EAF2 up-regulates transcription of RAS cascade genes including Grb2, PI3K, and BRAF, leading to elevated p-ERK levels, which may represent a major functional role of U19/EAF2 in the prostate. Furthermore, these observations suggest that U19/EAF2 is a key player in crosstalk between androgen receptor and the RAS-BRAF-ERK signaling pathway.

Citing Articles

EAF2: a tumor suppressor gene with multi-aspect functions.

Ji W, Cui C, Wang Y Front Pharmacol. 2024; 15:1440511.

PMID: 39588149 PMC: 11586179. DOI: 10.3389/fphar.2024.1440511.

Sequence, structural and functional conservation among the human and fission yeast ELL and EAF transcription elongation factors.

Sweta K, Dabas P, Sharma N Mol Biol Rep. 2021; 49(2):1303-1320.

PMID: 34807377 DOI: 10.1007/s11033-021-06958-x.

Regulation of ELL2 stability and polyubiquitination by EAF2 in prostate cancer cells.

Yang T, Jing Y, Dong J, Yu X, Zhong M, Pascal L Prostate. 2018; 78(15):1201-1212.

PMID: 30009504 PMC: 6537586. DOI: 10.1002/pros.23695.

EAF2 and p53 Co-Regulate STAT3 Activation in Prostate Cancer.

Pascal L, Wang Y, Zhong M, Wang D, Chakka A, Yang Z Neoplasia. 2018; 20(4):351-363.

PMID: 29518696 PMC: 5909677. DOI: 10.1016/j.neo.2018.01.011.

Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia.

Pascal L, Masoodi K, Liu J, Qiu X, Song Q, Wang Y J Endocrinol. 2017; 235(2):123-136.

PMID: 28870994 PMC: 5679084. DOI: 10.1530/JOE-17-0112.

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