The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

The lysine specific demethylase-1 (LSD1/KDM1A) regulates VEGF-A expression in prostate cancer

På svenska

Author

  • Vasundhra Kashyap
  • Shafqat Ahmad
  • Emeli M. Nilsson
  • Leszek Helczynski
  • Sinead Kenna
  • Jenny L Persson
  • Lorraine J. Gudas
  • Nigel P. Mongan

Summary, in English

Recurrent prostate cancer remains a major clinical challenge. The lysine specific demethylase-1 (LSD1/KDM1A), together with the JmjC domain-containing JMJD2A and JMJD2C proteins, have emerged as critical regulators of histone lysine methylation. The LSD1-JMJD2 complex functions as a transcriptional co-regulator of hormone activated androgen and estrogen receptors at specific gene promoters. LSD1 also regulates DNA methylation and p53 function. LSD1 is overexpressed in numerous cancers including prostate cancer through an unknown mechanism. We investigated expression of the LSD1 and JMJD2A in malignant human prostate specimens. We correlated LSD1 and JMJD2A expression with known mediators of prostate cancer progression: VEGF-A and cyclin A1. We show that elevated expression of LSD1, but not JMJD2A, correlates with prostate cancer recurrence and with increased VEGF-A expression. We show that functional depletion of LSD1 expression using siRNA in prostate cancer cells decreases VEGF-A and blocks androgen induced VEGF-A, PSA and Tmprss2 expression. We demonstrate that pharmacological inhibition of LSD1 reduces proliferation of both androgen dependent (LnCaP) and independent cell lines (LnCaP: C42, PC3). We show a direct mechanistic link between LSD1 overexpression and increased activity of pro-angiogenic pathways. New therapies targeting LSD1 activity should be useful in the treatment of hormone dependent and independent prostate cancer. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Department/s

Publishing year

2013

Language

English

Pages

555-566

Publication/Series

Molecular Oncology

Volume

7

Issue

3

Document type

Journal article

Publisher

Elsevier

Topic

  • Cancer and Oncology

Keywords

  • Epigenetic
  • Biomarker
  • Urological
  • Angiogenesis
  • Chromatin
  • Recurrence

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Pathology, Malmö
  • Experimental Cancer Research, Malmö

ISBN/ISSN/Other

  • ISSN: 1574-7891