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Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer.

Tassidis, Helena LU ; Brokken, Leon LU ; Jirström, Karin LU ; Ehrnström, Roy LU ; Pontén, Fredrik LU ; Ulmert, David LU ; Bjartell, Anders LU ; Härkönen, Pirkko LU and Gjörloff Wingren, Anette LU (2010) In International Journal of Cancer 126. p.2296-2307
Abstract
The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP... (More)
The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation whereas in SHP-1-silenced LNCaP cells IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer. (c) 2009 UICC. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
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in
International Journal of Cancer
volume
126
pages
2296 - 2307
publisher
John Wiley & Sons
external identifiers
  • wos:000276928700004
  • pmid:19795453
  • scopus:77951239460
ISSN
0020-7136
DOI
10.1002/ijc.24917
language
English
LU publication?
yes
id
14e3a067-d3a7-4473-a6b4-44fa30e5e54d (old id 1500822)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19795453?dopt=Abstract
date added to LUP
2009-11-04 11:08:56
date last changed
2018-06-17 04:57:16
@article{14e3a067-d3a7-4473-a6b4-44fa30e5e54d,
  abstract     = {The protein tyrosine kinase (PTK) receptors and cytosolic signaling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in regulation of growth of the benign and malignant prostate gland. Here we studied expression of the protein tyrosine phosphatase SHP-1 in prostate cancer cell lines and in human prostatic tissues. SHP-1 is expressed at a high level in LNCaP prostate cancer cells compared with PC3 cells. Silencing of SHP-1 expression with siRNA in LNCaP cells led to an increased rate of proliferation, whereas overexpression of SHP-1 by means of transient transfection in PC3 cells led to a decrease in proliferation. Corresponding changes were observed in cyclin D1 expression. We further demonstrate that LNCaP and PC3 cells respond differently to IL-6 stimulation. SHP-1 overexpression in PC3 cells reversed IL-6 stimulation of proliferation whereas in SHP-1-silenced LNCaP cells IL-6 inhibition of proliferation was not affected. In addition, IL-6 treatment led to higher levels of phosphorylated STAT3 in SHP-1-silenced LNCaP cells than in control cells. Next, SHP-1 expression in human prostate cancer was analyzed by immunohistochemical staining of tissue microarrays comprising tumor specimens from 100 prostate cancer patients. We found an inverse correlation between the tumor level of SHP-1 expression and time to biochemical recurrence and clinical progression among prostate cancer patients. In conclusion, our results suggest that a decreased level of SHP-1 expression in prostate cancer cells is associated with a high proliferation rate and an increased risk of recurrence or clinical progression after radical prostatectomy for localized prostate cancer. (c) 2009 UICC.},
  author       = {Tassidis, Helena and Brokken, Leon and Jirström, Karin and Ehrnström, Roy and Pontén, Fredrik and Ulmert, David and Bjartell, Anders and Härkönen, Pirkko and Gjörloff Wingren, Anette},
  issn         = {0020-7136},
  language     = {eng},
  pages        = {2296--2307},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Immunohistochemical detection of tyrosine phosphatase SHP-1 predicts outcome after radical prostatectomy for localized prostate cancer.},
  url          = {http://dx.doi.org/10.1002/ijc.24917},
  volume       = {126},
  year         = {2010},
}