Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

The role of PTPRK and PTPRM in prostate and breast cancer

Sun, Ping-Hui 2013. The role of PTPRK and PTPRM in prostate and breast cancer. PhD Thesis, Cardiff University.
Item availability restricted.

[thumbnail of 2013 SUNPHphd.pdf]
Preview
PDF - Accepted Post-Print Version
Download (7MB) | Preview
[thumbnail of 2013 SUNPH_THESIS PUBLICATION FORM.pdf] PDF - Additional Metadata
Restricted to Repository staff only

Download (332kB)

Abstract

Protein tyrosine phosphatases (PTPs) have been identified that mediate a range of physiological and pathological processes, such as proliferation and tumour metastasis. PTPRK and PTPRM belong to the same subfamily of PTPs. This study aims to investigate the role of PTPRK and PTPRM in cancer development and progression. Knockdown of PTPRK expression was performed in PC-3 and DU-145 cells. Functional assays were then carried out on these cells in order to determine any changes in their biological properties. Knockdown of PTPRK significantly reduced the growth and adhesion of both PC-3 and DU-145 cells. The experimental results suggested that reduction of cell growth is potential involvement of p53 and/or caspase-3 and -8 and its up-stream molecule JNK. The decreased expression of PTPRK and PTPRM are associated with poor prognosis and reduced survival. Knockdown of PTPRK resulted in increased adhesive and invasive abilities, and promoted cell proliferation and motility of breast cancer cells. Moreover, PTPRM knockdown resulted in elevated adhesion, invasion, and proliferation of breast cancer cells. Activation of ERK and JNK by tyrosine phosphorylation and consequent elevated MMP9 activity is involved in increased cell migration and invasion by PTPRM knockdown. These results suggested that PTPRK and PTPRM are involved in the disease progression of prostate and breast cancer by regulating a complex network of pathways and molecules. This provides further proof of the importance of the R2B subfamily, a subgroup of PTP superfamily, in cancer. In addition, it sheds some light on the use of PTPs as prognostic indicators of disease, aiding in diagnosis and treatment. The major effect is the promotion of motility and invasiveness of cancer cells via ERK and JNK pathways. However it can also impair the apoptosis mediated by JNK pathways in certain cancer cells, such as prostate cancer cells. Such contrasting effects on survival and motility require further investigation, and should also be considered when treating cancers by targeting these molecules.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Date of First Compliant Deposit: 30 March 2016
Last Modified: 15 Nov 2016 04:33
URI: https://orca.cardiff.ac.uk/id/eprint/46639

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics