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Role of the ProteinTyrosine Phosphatase SHP-I in Interleukin-6 Regulation of Prostate Cancer Cells

Tassidis, Helena LU ; Culig, Zoran ; Gjörloff Wingren, Anette LU and Härkönen, Pirkko LU (2010) In The Prostate 70(14). p.1491-1500
Abstract
BACKGROUND. Interleukin-6 (IL-6) is a multifunctional cytokine that has been implicated in the modulation of growth and progression of prostate cancer. Decreased expression of the tyrosine phosphatase SHP-1, involved in regulation of cytokine and tyrosine kinase receptor signaling, has been shown to be associated with less favorable outcome among prostate cancer patients. METHODS. Parental LNCaP cells and an LNCaP-IL6+subline, derived from parental LNCaP cells by continuous culture of the cells in the presence of recombinant IL-6 were used in the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP-1 was analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative PCRs, and reverse transcriptase PCRs.... (More)
BACKGROUND. Interleukin-6 (IL-6) is a multifunctional cytokine that has been implicated in the modulation of growth and progression of prostate cancer. Decreased expression of the tyrosine phosphatase SHP-1, involved in regulation of cytokine and tyrosine kinase receptor signaling, has been shown to be associated with less favorable outcome among prostate cancer patients. METHODS. Parental LNCaP cells and an LNCaP-IL6+subline, derived from parental LNCaP cells by continuous culture of the cells in the presence of recombinant IL-6 were used in the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP-1 was analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative PCRs, and reverse transcriptase PCRs. Proliferation and apoptosis of transfected cells were analyzed by caspase3/7 assay and flow cytometry. RESULTS. Phosphorylation of ERK and STAT3 was increased in the LNCaP-IL6+ subline compared with LNCaP cells, whereas pAKT was decreased. Overexpression and inhibition experiments with SHP-1 siRNA showed that SHP-1 reduced proliferation and increased apoptosis in both cell lines. Microarray analysis revealed 80 up-regulated and 87 down-regulated SHP-1-related genes in the LNCaP-IL6+ cell line compared with LNCaP cells. CONCLUSIONS. SHP-1 suppresses growth and increases apoptosis in both LNCaP and LNCaP-IL6+ cells, which suggests that SHP-1 could be a therapeutic target in prostate cancer, even when there is an IL-6-related growth advantage. Prostate 70: 1491-1500, 2010. (C) 2010 Wiley-Liss, Inc. (Less)
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; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
prostate cancer cells, apoptosis, proliferation, IL-6, PTEN
in
The Prostate
volume
70
issue
14
pages
1491 - 1500
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000282405700001
  • other:http://www.ncbi.nlm.nih.gov/pubmed/20687222?dopt=Abstract
  • scopus:77957007177
  • pmid:20687222
ISSN
0270-4137
DOI
10.1002/pros.21184
language
English
LU publication?
yes
additional info
Department affilation moved from v1000588 (Tumour Biology, Malmö) to v1000562 (Department of Translational Medicine) on 2016-01-18 14:39:29.
id
88239a7a-0bd0-4737-8e3c-e0606a94cd06 (old id 1694132)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20687222?dopt=Abstract
date added to LUP
2016-04-01 11:15:43
date last changed
2020-08-26 01:41:26
@article{88239a7a-0bd0-4737-8e3c-e0606a94cd06,
  abstract     = {BACKGROUND. Interleukin-6 (IL-6) is a multifunctional cytokine that has been implicated in the modulation of growth and progression of prostate cancer. Decreased expression of the tyrosine phosphatase SHP-1, involved in regulation of cytokine and tyrosine kinase receptor signaling, has been shown to be associated with less favorable outcome among prostate cancer patients. METHODS. Parental LNCaP cells and an LNCaP-IL6+subline, derived from parental LNCaP cells by continuous culture of the cells in the presence of recombinant IL-6 were used in the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP-1 was analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative PCRs, and reverse transcriptase PCRs. Proliferation and apoptosis of transfected cells were analyzed by caspase3/7 assay and flow cytometry. RESULTS. Phosphorylation of ERK and STAT3 was increased in the LNCaP-IL6+ subline compared with LNCaP cells, whereas pAKT was decreased. Overexpression and inhibition experiments with SHP-1 siRNA showed that SHP-1 reduced proliferation and increased apoptosis in both cell lines. Microarray analysis revealed 80 up-regulated and 87 down-regulated SHP-1-related genes in the LNCaP-IL6+ cell line compared with LNCaP cells. CONCLUSIONS. SHP-1 suppresses growth and increases apoptosis in both LNCaP and LNCaP-IL6+ cells, which suggests that SHP-1 could be a therapeutic target in prostate cancer, even when there is an IL-6-related growth advantage. Prostate 70: 1491-1500, 2010. (C) 2010 Wiley-Liss, Inc.},
  author       = {Tassidis, Helena and Culig, Zoran and Gjörloff Wingren, Anette and Härkönen, Pirkko},
  issn         = {0270-4137},
  language     = {eng},
  number       = {14},
  pages        = {1491--1500},
  publisher    = {John Wiley and Sons Inc.},
  series       = {The Prostate},
  title        = {Role of the ProteinTyrosine Phosphatase SHP-I in Interleukin-6 Regulation of Prostate Cancer Cells},
  url          = {http://dx.doi.org/10.1002/pros.21184},
  doi          = {10.1002/pros.21184},
  volume       = {70},
  year         = {2010},
}