Posibles efectos patogénicos del XMRV en cancer de próstata

[elipoarch]

[t]XMRV INFECTION INDUCES HOST GENES THAT REGULATE INFLAMMATION AND CELLULAR PHYSIOLOGY[/t]
Michael Lee*, Elona Gusho, Jaydip Das Gupta, Eric Klein, Robert Silverman, Cleveland, OH
The Journal of Urology
Volume 185, Issue 4, Supplement, Page e113,
April 2011

INTRODUCTION AND OBJECTIVES

XMRV is a novel human retrovirus associated with
prostate cancer. Although other gammaretroviruses
cause cancer in animals, it remains unknown if XMRV
is a cause of disease.

However, indirect or direct modes of carcinogenesis
by XMRV have been suggested depending on whether
the virus was found in stroma or malignant
epithelium.

To gain insight into the possible role of XMRV in
these diseases we have identified genes that are
induced in response to XMRV infection.



METHODS

Prostate cancer cell line DU145 was infected for 8,
24, 48 and 120h with XMRV. A comparison to
uninfected DU145 cells cultured for the same periods
of time served as controls.

A population of total RNA was isolated using Qiagen
RNeasy Mini Kit followed by digestion of DNA with
DNAse treatment.

XMRV infections at the different time points were
monitored using real-time RT-PCR for env XMRV RNA.

The RNA samples were analyzed for gene expression
using Sentrix humanRef-8 v3 expression bead chips
from Illumina (Cleveland Clinic Genomics Core).

To verify the results obtained by the array
experiment, we determined induction of a subset of
the regulated genes.

Total RNA was reverse transcribed to cDNA using
iScript Select cDNA Synthesis Kit from Bio-Rad
(random primers method).

Induction of selected genes by XMRV infection was
verified by qPCR (Relative Quantification) from the
cDNA pool using SYBR Green master mix.

Fold-induction at each time point for the individual
mRNAs was determined.

In addition, pathway predictions were determined
using Ingenuity Systems (content version 3002)
software for genes induced by more than 2-fold
following XMRV infection.


RESULTS

In gene expression profiling, we observed maximal
gene induction between 24 and 48 h post-infection.

For example, the pro-inflammatory cytokine IL8
gene, a potential contributing factor to androgen
independent growth of late-stage prostate cancer,
was consistently induced by XMRV infection by up to
6-fold.

Of the XMRV induced genes, pathway analysis
indicated 10 genes are implicated in cell morphology,
11 genes in cellular development, 12 genes in
cell-to-cell signaling and interaction, 11 genes in
cellular movement and 13 genes in cellular growth
and proliferation.



CONCLUSIONS

The chemokine IL-8 is one of the most highly
induced genes in response to XMRV infection of
prostate cancer cell line DU145.

XMRV induction of the 30 host genes identified in
this study suggests a profound effect of the virus on
fundamental cellular physiology and inflammation.

These findings could be relevant to the possible
pathogenic effects on XMRV in prostate cancer.

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[EndSFC]

Bueno, finalmente alguna evidencia de patogeneidad! El XMRV, induce la expresión de la IL-8, además de otros genes estudiados relacionados con la fisiología básica celular. Este "bichejo" parece no es tan "majo" como se pensaba!