ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression

Oncotarget
Takashi KawaharaHiroshi Miyamoto

Abstract

Little is known about biological significance of ELK1, a transcriptional factor that activates downstream targets including c-fos proto-oncogene, in bladder cancer. Recent preclinical evidence also suggests the involvement of androgen receptor (AR) signaling in bladder cancer progression. In this study, we aim to investigate the functions of ELK1 in bladder cancer growth and their regulation by AR signals. Immunohistochemistry in bladder tumor specimens showed that the levels of phospho-ELK1 (p-ELK1) expression were significantly elevated in urothelial neoplasms, compared with non-neoplastic urothelium tissues, and were also correlated with AR positivity. Patients with p-ELK1-positive non-muscle-invasive and muscle-invasive tumors had significantly higher risks for tumor recurrence and progression, respectively. In AR-positive bladder cancer cell lines, dihydrotestosterone treatment increased ELK1 expression (mRNA, protein) and its nuclear translocation, ELK1 transcriptional activity, and c-fos expression, which was restored by an anti-androgen hydroxyflutamide. ELK1 silencing via short hairpin RNA (shRNA) resulted in decreases in cell viability/colony formation, and cell migration/invasion as well as an increase in apoptosis. ...Continue Reading

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Citations

Jan 16, 2016·Disease Markers·Hiroki Ide, Hiroshi Miyamoto
Aug 8, 2020·Cancers·Hiroki Ide, Hiroshi Miyamoto
Nov 17, 2016·Oncotarget·Martyn BullockRoderick J Clifton-Bligh
Mar 1, 2017·Cancers·Peng LiHiroshi Miyamoto
Jul 23, 2016·Oncotarget·Takashi KawaharaHiroshi Miyamoto
Mar 9, 2018·International Journal of Molecular Sciences·Satoshi InoueHiroshi Miyamoto
May 8, 2018·The Journal of Urology·Ville J MäkeläTeemu J Murtola
Jun 4, 2019·International Journal of Molecular Sciences·Hiroshi Miyamoto
Dec 7, 2018·Endocrine Connections·Satoshi InoueHiroshi Miyamoto
May 5, 2017·Molecular Cancer Therapeutics·Michael A GordonJennifer K Richer
May 4, 2018·Molecular Cancer Therapeutics·Hiroki IdeHiroshi Miyamoto
Nov 15, 2019·The Aging Male : the Official Journal of the International Society for the Study of the Aging Male·Aram KimSung Hyun Paick
Nov 20, 2020·Environmental Research·Eve PellerinMartin Pelletier

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Methods Mentioned

BETA
dissection
nuclear translocation
transfection
flow cytometry
xenograft
PCR
electrophoresis
fluorescence microscopy
Assay

Software Mentioned

Guava Cell Cycle
ImageJ
EVOS

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