Monday, October 17, 2011

XMRV doesn't exist ... but it causes prostate cancer

While one cadre of scientists is loudly proclaiming that XMRV cannot possibly cause CFS because it's only a lab contaminant, another is proving that it does exist, and does cause prostate cancer.  How much of this debate is really about sexism rather than science?
 

http://bit.ly/mZJDTo

The Prostate

Original Article

XMRV accelerates cellular proliferation,
transformational activity, and invasiveness
of prostate cancer cells by downregulating
p27Kip1

Jui Pandhare-Dash1,2, Chinmay K. Mantri1,2, Yuanying
Gong2, Zhenbang Chen2, Chandravanu Dash1,2,*

Article first published online: 19 SEP 2011

DOI: 10.1002/pros.21491

Copyright © 2011 Wiley-Liss, Inc.

Keywords: XMRV;p27Kip1;CDK;miR221/222;MMP


Abstract

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.






No comments: