Piwil2 expression selects for known stem-cell and cancer stem-cell markers in LNCaP prostate cancer cell line


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Deepali Pal (1), Craig Robson (1), Stuart Williamson (1), Karim Nayernia (2), Hamid Reza Soleimanpour-Lichaei (2), Rakesh Heer (1)
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom (1), North East England Stem Cell Institute, Newcastle University, Newcastle upon Tyne, United Kingdom (2)

Background

Cancer stem cells are a subpopulation of cancer cells that drive production of the rest of the tumour. In particular, aberrant stem-cell renewal has been implicated in carcinogenesis. The genes of the piwi family are highly conserved during evolution and are involved in stem-cell self-renewal in different organisms. One such member of the piwi family, the Piwil2 is a germ-cell specific protein and has been documented to be expressed in an increasing number of cancers. In this study we explored the effects of Piwil2 gene over-expression in LNCaP human prostate cancer cells. 

Method

 Real time PCR was employed to study the effect of this gene on the transcription of known stem cell and prostate specific differentiation markers that have also been implicated in carcinogenesis. Immunohistochemistry studies on human cancer prostate material for Piwil2 expression was also performed.    

Results

LNCaP cells over expressing Piwil2 , compared with wild type LNCaP, demonstrated higher levels of  stem cell specific markers (Oct-4, SOX-2, LIN28 and NANOG) and expression of prostate specific stem cell markers (CD133, CD117, CD44, Nkx3.1). Furthermore, Piwil2 expression was seen to potentiate androgen receptor function, which is known to be an integral pathway in prostate cancer progression.  In addition, we have shown that piwi expression in human prostate cancer material is present through immunohistochemistry and we are currently investigating its correlation with grade, stage and prognosis. 

Conclusion

 In summary, we demonstrated induction of a stem-cell phenotype in LNCaP with Piwil2 over expression. Understanding the importance of this gene in regulating prostate cancer stem cells requires additional investigation and our data for now highlights an attractive potential role for piwil2 as a candidate for use in prostate cancer therapeutics and as a prognostic marker. 

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