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Expression and function of the protein tyrosine phosphatases SHP-1 and SHP-2 in prostate cancer

Tassidis, Helena LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:24.
Abstract
Prostate cancer is one of the most frequent cancers in males in Western countries. Radical prostatectomy serves as the first line of treatment for patients with localised prostate cancer. However, in many cases the cancer will recur. It is currently difficult to identify those patients at a high risk of tumour recurrence. Therefore, molecular markers associated with and predicting disease recurrence are needed to help identify patients and to better understand the signalling pathways in prostate cancer cells. The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in the regulation of growth of the benign and malignant prostate gland. Here, we... (More)
Prostate cancer is one of the most frequent cancers in males in Western countries. Radical prostatectomy serves as the first line of treatment for patients with localised prostate cancer. However, in many cases the cancer will recur. It is currently difficult to identify those patients at a high risk of tumour recurrence. Therefore, molecular markers associated with and predicting disease recurrence are needed to help identify patients and to better understand the signalling pathways in prostate cancer cells. The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in the regulation of growth of the benign and malignant prostate gland. Here, we have studied the expression and function of the PTP SHP-1 in prostate cancer cell lines and in clinical material from patients that underwent radical prostatectomy. We have also analysed the expression of SHP-2 in prostate cancer cell lines and human prostate cancer tissue.



We performed several different in vitro and in vivo experiments that were evaluated with methods such as immunohistochemical staining of tissue micro arrays (TMA), polymerase chain reaction (PCR), Western blot, eukaryotic cell transfections, proliferation assays, PTP enzymatic activity assay, caspase assay, flow cytometric assays, cell growth in vivo in nude mice, migration and invasion assays.



Our results show that a low or absent SHP-1 expression might serve as a marker to identify prostate cancer patients at an increased risk of tumour recurrence. We also demonstrate that proliferation and apoptosis can be regulated by modulations of the SHP-1 expression in prostate cancer cells. SHP-1 expression and activity is reduced in the LNCaP cell line that was long-term stimulated with IL-6, showing that the cytokine might regulate SHP-1 activity. SHP-1 is also able to reduce growth of PC3 cells growing in vivo in nude mice. These results suggest that SHP-1 is a negative modulator by inhibiting prostate cancer cell proliferation through the growth factor and cytokine-induced pathways in prostate cancer cells. Our results also suggest that SHP-2 may have similar activity in prostate cancer. (Less)
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author
supervisor
opponent
  • docent Wikström, Pernilla, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Prostate cancer SHP-1 SHP-2 IL-6 phosphorylation signalling pathways
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:24
pages
127 pages
publisher
Lund University, Faculty of Medicine
defense location
MFC entrance 59, Malmö University Hospital
defense date
2010-03-26 09:00
ISSN
1652-8220
ISBN
978-91-86443-38-2
language
English
LU publication?
yes
id
6ca27a5a-7f2f-4b0a-978b-44ac8718fe84 (old id 1553617)
date added to LUP
2010-03-10 10:40:24
date last changed
2018-05-29 09:31:17
@phdthesis{6ca27a5a-7f2f-4b0a-978b-44ac8718fe84,
  abstract     = {Prostate cancer is one of the most frequent cancers in males in Western countries. Radical prostatectomy serves as the first line of treatment for patients with localised prostate cancer. However, in many cases the cancer will recur. It is currently difficult to identify those patients at a high risk of tumour recurrence. Therefore, molecular markers associated with and predicting disease recurrence are needed to help identify patients and to better understand the signalling pathways in prostate cancer cells. The protein tyrosine kinase (PTK) receptors and cytosolic signalling proteins as well as the protein tyrosine phosphatases (PTPs) have important roles in the regulation of growth of the benign and malignant prostate gland. Here, we have studied the expression and function of the PTP SHP-1 in prostate cancer cell lines and in clinical material from patients that underwent radical prostatectomy. We have also analysed the expression of SHP-2 in prostate cancer cell lines and human prostate cancer tissue. <br/><br>
<br/><br>
We performed several different in vitro and in vivo experiments that were evaluated with methods such as immunohistochemical staining of tissue micro arrays (TMA), polymerase chain reaction (PCR), Western blot, eukaryotic cell transfections, proliferation assays, PTP enzymatic activity assay, caspase assay, flow cytometric assays, cell growth in vivo in nude mice, migration and invasion assays.<br/><br>
<br/><br>
Our results show that a low or absent SHP-1 expression might serve as a marker to identify prostate cancer patients at an increased risk of tumour recurrence. We also demonstrate that proliferation and apoptosis can be regulated by modulations of the SHP-1 expression in prostate cancer cells. SHP-1 expression and activity is reduced in the LNCaP cell line that was long-term stimulated with IL-6, showing that the cytokine might regulate SHP-1 activity. SHP-1 is also able to reduce growth of PC3 cells growing in vivo in nude mice. These results suggest that SHP-1 is a negative modulator by inhibiting prostate cancer cell proliferation through the growth factor and cytokine-induced pathways in prostate cancer cells. Our results also suggest that SHP-2 may have similar activity in prostate cancer.},
  author       = {Tassidis, Helena},
  isbn         = {978-91-86443-38-2},
  issn         = {1652-8220},
  keyword      = {Prostate cancer 
SHP-1
SHP-2 
IL-6
phosphorylation
signalling pathways},
  language     = {eng},
  pages        = {127},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Expression and function of the protein tyrosine phosphatases SHP-1 and SHP-2 in prostate cancer},
  volume       = {2010:24},
  year         = {2010},
}