XMRV establishes an efficient spreading infection etc. in prostate carcinoma cells

Dolphin

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Full title:
Xenotropic murine leukemia virus-related virus establishes an efficient spreading infection and exhibits enhanced transcriptional activity in prostate carcinoma cells

(Apologies if this has been posted before. I searched the forum but just saw a mention of its title, not the abstract or link to full text. I don't follow the XMRV forum that closely)

Full free text at:
http://jvi.asm.org/cgi/content/full/84/5/2556
or
http://jvi.asm.org/cgi/reprint/84/5/2556 (Pdf version)


J Virol. 2010 Mar;84(5):2556-62. Epub 2009 Dec 16.

Xenotropic murine leukemia virus-related virus establishes an efficient spreading infection and exhibits enhanced transcriptional activity in prostate carcinoma cells.

Rodriguez JJ, Goff SP.

Columbia University, Howard Hughes Medical Institute, HHSC 1310c, New York, New York 10032, USA.

(I've given each line its own paragraph)

Xenotropic murine leukemia virus-related virus (XMRV) is a novel human gammaretrovirus discovered in association with human prostate tumors.

XMRV was first identified in prostate stromal cells surrounding the tumors of patients carrying a mutation in the HPC1 gene locus.

To determine the tropism of XMRV in cell culture, we tested the ability of XMRV to spread and replicate in various prostate and nonprostate cell lines.

We found that although the expression of XMRV viral proteins and the spread of infectious virus were minimal in a variety of cell lines, XMRV displayed robust expression and infection in LNCaP prostate tumor cells.

The transcriptional activity of the XMRV long terminal repeat (LTR) was found to be higher than the Moloney murine leukemia virus LTRs in both LNCaP and WPMY-1 (simian virus 40-transformed prostate stromal cells).

The U3 promoter of XMRV and a glucocorticoid response element (GRE) within the U3 were required for the transcriptional activity in LNCaP cells.

Coexpression of the androgen receptor and stimulation with dihydrotestosterone stimulated XMRV-LTR-dependent transcription in 293T cells, and the GRE was required for this activity.

These data suggest that XMRV may replicate more efficiently in LNCaP cells in part due to the transcriptional environment in LNCaP cells.

PMID: 20015990
 

Advocate

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Hi Tom,

I always have to look up LNCaP. For others in the same boat, this is from Wikipedia:

LNCap cells are a cell line of human cells commonly used in the field of oncology. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells derived from the left supraclavicular lymph node metastasis from a 50-year-old caucasian male in 1977. They are adherent epithelial cells growing in aggregates and as single cells.
 

ukxmrv

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I think this was mentioned on the other threads about the shortcomings of the UK papers. They didn't use LnCAP but Dr Mikovits said in one of the talks or papers that this should be used to grow the virus before looking for it? LnCAP sounds like a "must have" for any serious replication project.
 

Dolphin

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Thanks Advocate and ukxmrv. I only have so much mental energy and I stopped studying biology at age 16 [I studied single honor Mathematics in college (in Trinity College Dublin, we didn't have the option of picking from other fields unlike say US colleges)] so probably will leave this thread to you and others.
 

Mithriel

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This is a very important paper. I think some of the studies that didn't find XMRV in prostrate cancer patients didn't use this cell line.

This is what always happens with a new discovery. The best way of working with an organism is gradually teased out.

Mithriel
 

CBS

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For those who didn't have a chance to listen to the interview given by Dr. Goff at the recent CROI conference (http://blip.tv/file/3242252), I was very impressed with Dr. Goff's careful description of the work and his 35 years of studying this retrovirus in the lab. He was careful to say that there is a lot to be learned as they know so little about how XMRV behaves in humans and whether or not it plays a role in human disease (more knowledge about how it behaves in a petri dish - which is a good thing).

In the face of all that caution, it is encouraging to know that Dr. Goff is in the process of conducting (or least preparing to conduct - I don't know if data collection has started) a study of XMRV in patients with CFS. He's a good person to have interested in XMRV and a possible link to CFS.