XMRV accelerates cellular proliferation and invasiveness of prostate cancer cells

[Jemal]

This seems to be an important part of the puzzle.

XMRV accelerates cellular proliferation, transformational activity, and invasiveness of prostate cancer cells by downregulating p27Kip1
Jui Pandhare-Dash, Chinmay K. Mantri, Yuanying Gong, Zhenbang Chen, Chandravanu Dash

Article first published online: 19 SEP 2011

BACKGROUND
Xenotropic murine leukemia virus-related retrovirus (XMRV) is a recently discovered gammaretrovirus that was originally detected in prostate tumors. However, a causal relationship between XMRV and prostate cancer remains controversial due to conflicting reports on its etiologic occurrence. Even though gammaretroviruses are known to induce cancer in animals, a mechanism for XMRV-induced carcinogenesis remains unknown. Several mechanisms including insertional mutagenesis, proinflammatory effects, oncogenic viral proteins, immune suppression, and altered epithelial/stromal interactions have been proposed for a role of XMRV in prostate cancer. However, biochemical data supporting any of these mechanisms are lacking. Therefore, our aim was to evaluate a potential role of XMRV in prostate carcinogenesis.

METHODS
Growth kinetics of prostate cancer cells are conducted by MTT assay. In vitro transformation and invasion was carried out by soft agar colony formation, and Matrigel cell invasion assay, respectively. p27Kip1 expression was determined by Western blot and MMP activation was evaluated by gelatin-zymography. Up-regulation of miR221 and miR222 expression was examined by real-time PCR.

RESULTS
We demonstrate that XMRV infection can accelerate cellular proliferation, enhance transformation, and increase invasiveness of slow growing prostate cancer cells. The molecular basis of these viral induced activities is mediated by the downregulation of cyclin/cyclin dependent kinase inhibitor p27Kip1. Downstream analyses illustrated that XMRV infection upregulates miR221 and miR222 expression that target p27Kip1 mRNA.

CONCLUSIONS
We propose that downregulation of p27Kip1 by XMRV infection facilitates transition of G1 to S, thereby accelerates growth of prostate cancer cells. Our findings implicate that if XMRV is present in humans, then under appropriate cellular microenvironment it may serve as a cofactor to promote cancer progression in the prostate. Prostate 2011 Wiley-Liss, Inc.

http://onlinelibrary.wiley.com/doi/10.1002/pros.21491/abstract

 

[eric_s]

That's very interesting, thanks. It makes the contaminant theory less likely, at least in prostate cancer. And if in prostate cancer it's not a contaminant, then why should it be in ME/CFS. But of course we need to wait for further results.

My feeling is that this is a very nasty virus, because it's hard to detect, doesn't have any spectacular, quick effects that make you realize it's there immediately and over time it might have different sorts of "small" effects that lead to different dieases, depending on where it is and maybe also depending on the host. This is really just my gut feeling, nothing more, now it's up to science to find out what it really does.

 

[Jemal]

My feeling is that this is a very nasty virus, because it's hard to detect, doesn't have any spectacular, quick effects that make you realize it's there immediately and over time it might have different sorts of "small" effects that lead to different dieases, depending on where it is and maybe also depending on the host. This is really just my gut feeling, nothing more, now it's up to science to find out what it really does.

I agree with you Eric. Especially the slow onset of symptoms is very dangerous. It could take years or even decades, before someone falls ill. This means the virus could have gone unnoticed for many years and even if discovered it would be very hard to link it to certain diseases. Which could be what is happening now...

 

[Bob]

I've only just spotted this paper... Interesting... I suppose it could potentially be relevant to lymphomas as well as prostate cancer.

 

[Enid]

Very interesting - thanks Jemal - another bit of the puzzle. Nothing over with XMRV it seems.

 

[RustyJ]

A recent HIV study picked up variants of HIV with different pathologies, and MLV studies in mice show the same. I think it is likely that the prostate HGRV might prove to be different from the strain (strains) causing problems in ME/CFS patients. Eg, I can't recall any record of neurological symptoms in prostate cancer patients. This of course will add another layer of complexity to the problems besetting the field.