Research article summary (published 29 Sep 2009):

Nemo-like kinase induces apoptosis and inhibits androgen receptor signaling in prostate cancer cells.

Full Abstract

BACKGROUND: The mitogen-activated protein kinases (MAPKs) regulate cell growth, differentiation, and stress responses, and many critical signaling pathways are subject to cross-regulation by MAPK signaling. Previous studies have yielded evidence of cross-talk between the MAPK pathways and androgen receptor (AR) signaling, which plays a critical role in growth control of both normal prostate and prostate cancer (PCa). Objective of this study was to evaluate the expression of MAPK-like protein nemo-like kinase (NLK) in PCa and its effects on AR-mediated transcription. METHODS: Real-time PCR and IHC were used to evaluate levels of NLK in prostatic samples. Effects of over-expression of NLK on apoptosis and proliferation were determined using Western blot and flow cytometry. Effects on AR signaling were evaluated using over-expression and knockdown of NLK in PCa cells in combination with PCR, Western blotting and reporter assays. RESULTS: Our results show that the expression of NLK is decreased in PCa metastases in comparison to normal prostate epithelium and primary PCa. Our results also show that over-expression of NLK resulted in induction of apoptosis, which was more pronounced in AR-expressing LNCaP versus AR-negative PC-3 cells. Higher levels of NLK decreased levels of AR mRNA and protein as well as inhibited AR-mediated transcription. CONCLUSIONS: NLK expression is altered during PCa progression and it is involved in regulation of AR signaling in these cells. A deeper understanding of the roles of NLK in regulation of AR-mediated transcription and control of PCa progression may point the way to new modes of therapeutic intervention in this disease.

Author information

Author/s: Emami, Katayoon H (KH); Brown, Lisha G (LG); Pitts, Tiffany E M (TE); Sun, Xizhang (X); Vessella, Robert L (RL); Corey, Eva (E);

Affiliation: Department of Urology, University of Washington, Seattle, Washington 98195, USA.

Grants: 5R01CA125395 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Prostate (Prostate), published in United States. (Language: eng)

Reference: 2009-Oct; vol 69 (issue 14) : pp 1481-92

Dates: Created 2009/09/01; Completed 2009/09/23;

PMID: 19514049, status: MEDLINE (last retrieval date: 9/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Apoptosis - physiology CHO Cells Cell Division - physiology Cricetinae Cricetulus Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans

Intracellular Signaling Peptides and Proteins - genetics; metabolism MAP Kinase Signaling System - physiology Male Prostatic Neoplasms - metabolism; pathology Protein-Serine-Threonine Kinases - genetics; metabolism RNA, Messenger - metabolism Receptors, Androgen - genetics; metabolism Transcription, Genetic - physiology Transfection

Associated Chemicals: Intracellular Signaling Peptides and Proteins (0) ; RNA, Messenger (0) ; Receptors, Androgen (0) ; NLK protein, human (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)

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