Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • Metabolism Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Research
Molecular Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Rapid Impact Archive
    • Meeting Abstracts
    • Collections
      • Metabolism Collection
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
Research Article

The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells

Peder R Braadland, Håkon Ramberg, Helene Hartvedt Grytli, Alfonso Urbanucci, Heidi Kristin Nielsen, Ingrid Jenny Guldvik, Andreas Engedal, Kirsi Ketola, Wanzhong Wang, Aud Svindland, Ian G. Mills, Anders Bjartell and Kristin Austlid Tasken
Peder R Braadland
Institute for Cancer Research, Oslo University Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Peder R Braadland
Håkon Ramberg
Urology/Institute of Cancer Research, Oslo University Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helene Hartvedt Grytli
Institute for Cancer Research, Oslo University Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alfonso Urbanucci
Department of Tumor Biology, Oslo University Hospital, Institute for Cancer Research
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alfonso Urbanucci
Heidi Kristin Nielsen
Institute of Cancer Research/Department of Clinical Medicine, Oslo University Hospital/University of Oslo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ingrid Jenny Guldvik
Institute of Cancer Research, Oslo University Hospital
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Engedal
University of Oslo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kirsi Ketola
Institute of Biomedicine, University of Eastern Finland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wanzhong Wang
Department of Medical Biosciences, Umeå University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aud Svindland
Department of Pathology/Department of Clinical Medicine, Oslo University Hospital/University of Oslo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian G. Mills
Nuffield Department of Surgical Sciences, University of Oxford
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ian G. Mills
Anders Bjartell
Department of Urology and Department of Clinical Sciences, Division of Urological Cancers, Lund University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristin Austlid Tasken
Institute of Cancer Research/Department of Clinical Medicine, Oslo University Hospital/University of Oslo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: k.a.tasken@medisin.uio.no
DOI: 10.1158/1541-7786.MCR-18-0605
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

The incidence of treatment-related neuroendocrine (NE) prostate cancer (t-NEPC) is rising as more potent drugs targeting the androgen signaling axis are clinically implemented. Neuroendocrine transdifferentiation (NEtD), an putative initial step in t-NEPC development, is induced by androgen deprivation therapy (ADT) or anti-androgens, and by activation of the β2-adrenergic receptor (ADRB2) in prostate cancer cell lines. Thus, understanding whether ADRB2 is involved in ADT-initiated NEtD may assist in developing treatment strategies that can prevent or reverse t-NEPC emergence, thereby prolonging therapeutic responses. Here we found that in primary, treatment-naïve prostate cancers, ADRB2 mRNA was positively correlated with expression of luminal differentiation markers, and ADRB2 protein levels were inversely correlated with Gleason grade. ADRB2 mRNA was upregulated in metastatic prostate cancer, and progressively downregulated during androgen deprivation therapy (ADT) and t-NEPC emergence. In androgen-deprivated medium, high ADRB2 was required for LNCaP cells to undergo NEtD, measured as increased neurite outgrowth and expression of neuron differentiation and NE genes. ADRB2 overexpression induced an NE-like morphology in both AR positive and -negative prostate cancer cell lines. ADRB2 downregulation in LNCaP cells increased canonical Wnt signaling, and GSK3α/β inhibition reduced the expression of neuron differentiation and NE genes. In LNCaP xenografts, more pronounced castration-induced NEtD was observed in tumors derived from high than low-ADRB2 cells. In conclusion, high ADRB2 expression is required for ADT-induced NEtD, characterized by ADRB2 downregulation and t-NEPC emergence. Implications: This data suggest a potential application of β-blockers to prevent cancer cells committed to a neuroendocrine lineage from evolving into t-NEPC.

  • Received June 8, 2018.
  • Revision received April 25, 2019.
  • Accepted August 6, 2019.
  • Copyright ©2019, American Association for Cancer Research.

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't.
PreviousNext
Back to top

Published OnlineFirst August 8, 2019
doi: 10.1158/1541-7786.MCR-18-0605

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells
(Your Name) has forwarded a page to you from Molecular Cancer Research
(Your Name) thought you would be interested in this article in Molecular Cancer Research.
Citation Tools
The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells
Peder R Braadland, Håkon Ramberg, Helene Hartvedt Grytli, Alfonso Urbanucci, Heidi Kristin Nielsen, Ingrid Jenny Guldvik, Andreas Engedal, Kirsi Ketola, Wanzhong Wang, Aud Svindland, Ian G. Mills, Anders Bjartell and Kristin Austlid Tasken
Mol Cancer Res August 8 2019 DOI: 10.1158/1541-7786.MCR-18-0605

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells
Peder R Braadland, Håkon Ramberg, Helene Hartvedt Grytli, Alfonso Urbanucci, Heidi Kristin Nielsen, Ingrid Jenny Guldvik, Andreas Engedal, Kirsi Ketola, Wanzhong Wang, Aud Svindland, Ian G. Mills, Anders Bjartell and Kristin Austlid Tasken
Mol Cancer Res August 8 2019 DOI: 10.1158/1541-7786.MCR-18-0605
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • HMMR is regulated by galectin-3 and C/EBPβ
  • Cell Cycle Dependent Epigenetic Therapeutics for PDAC
  • PPARδ-YAP1-SOX9 axis in GC progression
Show more Research Article
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Rapid Impact Archive
  • Meeting Abstracts

Information for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About MCR

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2019 by the American Association for Cancer Research.

Molecular Cancer Research
eISSN: 1557-3125
ISSN: 1541-7786

Advertisement