The role of visfatin in prostate cancer
Patel, Snehal T. (2011) The role of visfatin in prostate cancer. MD thesis, University of Warwick.
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The aim of this study was to investigate the role of the adipokine visfatin as a possible
molecular mediator between obesity and prostate cancer.
Visfatin, an adipokine that is elevated in obesity and has many proposed roles and has
been linked to a variety of cancers. No data pertaining to the role of visfatin in prostate
cancer existed and this was an area that this study looked to address. It is suggested
that obesity is a significant risk factor for prostate cancer; in particular, aggressive
disease and adipokines have been investigated as a link for this hypothesis.
This study presents novel data demonstrating the expression of visfatin in the LNCaP
and PC3 cell lines as well as in benign and cancerous prostate tissue at both mRNA
and protein level. Furthermore visfatin is shown to have functional roles in autoregulation
and promoting increased cell proliferation in PC3 cells and also showed
further effects with respect to cell migration across a wound. These data gave promise
to develop the study further and evaluate potential mechanisms of action including
common second messenger systems such as MAPK and also other oncologically
multifunctional molecules in the forms of MMP-2/-9. We then demonstrated that visfatin
up-regulated MAPK phosphorylation and MMP mRNA/protein expression and more
importantly MMP-2/-9 zymographic activity. This provided possible mechanisms by
which visfatin may mediate a role for obesity driven aggressive prostate cancer.
The study then looked to evaluate NMN (the byproduct of visfatin catalysed
biosynthetic activity), as well as the visfatin inhibitor FK866 which is being evaluated as
chemotherapeutic agent. Unsurprisingly NMN and FK866 had opposing actions on
proliferation and FK866 was naturally proapoptotic. NMN was able to rescue the effect
of FK866 on PC3 cell apoptosis. Prior studies have shown that NMN did not affect
oncogenes however NMN was found to significantly reduce BAX mRNA expression in
The findings are consistent with other studies linking visfatin with cancer states. These
novel data indicate roles for visfatin in prostate cancer and possible mechanisms linking
obesity and prostate cancer.
|Item Type:||Thesis or Dissertation (MD)|
|Subjects:||R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)|
|Library of Congress Subject Headings (LCSH):||Prostate -- Cancer -- Etiology, Obesity|
|Official Date:||March 2011|
|Institution:||University of Warwick|
|Theses Department:||Warwick Medical School|
|Supervisor(s)/Advisor:||Randeva, Harpal Singh|
|Extent:||224,  leaves : ill., charts|
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