SCARY-- Mouse Mammary tumor virus shown present in/rapidly reproducing in humanbreast

[Lani]

in cultured cells, at least--should say spreading, not replicating (as that is the next experiment to be done)

OPEN ACCESS: Rapid spread of mouse mammary tumor virus in cultured human breast cells [Retrovirology]
Background: The role of mouse mammary tumor virus (MMTV) as a causative agent in human breast carcinogenesis has recently been the subject of renewed interest. The proposed model is based on the detection of MMTV sequences in human breast cancer but not in healthy breast tissue. One of the main drawbacks to this model, however, was that until now human cells had not been demonstrated to sustain productive MMTV infection.
Results: Here, we show for the first time the rapid spread of mouse mammary tumor virus, MMTV(GR), in cultured human mammary cells (Hs578T), ultimately leading to the infection of every cell in culture. The replication of the virus was monitored by quantitative PCR, quantitative RT-PCR and immunofluorescence imaging. The infected human cells expressed, upon cultivation with dexamethasone, MMTV structural proteins and released spiked B-type virions, the infectivity of which could be neutralized by anti-MMTV antibody. Replication of the virus was efficiently blocked by an inhibitor of reverse transcription, 3`-azido-3`-deoxythymidine. The human origin of the infected cells was confirmed by determining a number of integration sites hosting the provirus, which were unequivocally identified as human sequences.
Conclusions: Taken together, our results show that human cells can support replication of mouse mammary tumor virus.

[fauxgypsy]

Lani, has anyone looked at the efficacy of anti-viral compounds in breast cancer, or any cancer?

Leslie

[PinkGirl]

Lani, I read a similar article about MMTV being found in human breast tissue.
They are not sure how the virus transfers to humans. This article said that it was more likely from contamination rather than infection. I don't understand that. Hope Tiptoe isn't a carrier.

[Lani]

means the lab personnel, cleaning crew, etc may have inadvertently contaminated the samples with the virus.This is an old argument which this study refutes...if it was only contamination it would not spread to other cells.

The fine point is that they could show that the cells "support replication" but they have yet to show "functional replication" which is I think what their next experiment will attempt to prove.

Infection seems to have been proven, whether it can sustain itself with functional replication is next on their scientific agenda

[PinkGirl]

does anyone know how it transfers to humans? Does that mean we should stay away from mouse do-do in the dark corners of our garages?

[Linda]

My onc actually asked me if I'd been "sweeping barns" before my dx, and in fact we did have a mouse infestation in our house (which I cleaned up) the summer before I was dx. My onc clearly thinks that exposure to mouse droppings, etc, could have been the bc trigger ("could" is the operative word here...who knows...) Interesting...
Linda

[Hopeful]

Here is a link to a news article about this study: http://www.breastcancersource.com/breastcancersourcehcp/6096_28710___.aspx and the provisional pdf from which the article and the abstract Lani posted above are drawn: http://www.retrovirology.com/content/pdf/1742-4690-4-73.pdf

Hopeful

[Paris]

If they think this is true they should do a study of women who work with animals either in stables or zoos. I've spent my life riding horses and working in barns including one at my house but I wouldn't think that's why I got bc. My sister was diagnosed before me and she was not a horse person.

[Lani]

Is your sister her2+?

Thanks for the info,
Lani

[Paris]

Hi Lani,Yes my sister is HER2+ as well as ER/PR+.

Jamie

[Lani]

her2+ breast cancer, particularly those that are ER+

It is Xlinked and thus inherited from mother to daughter (although it may be involved in a severe immune deficiency when passed on to male children as FOXP3 is important for an immune system component called T regulatory cells)

There is not yet a clinically available test for FOXP3, but if we gather enough families with her2+ breast cancer, perhaps interest could be raised...


FOXP3 gene found to be involved in breast cancer

Medical Research News
Published: Sunday, 29-Jul-2007

Researchers at the University of Michigan Comprehensive Cancer Center have identified a gene linked to the development of an aggressive form of breast cancer.

The researchers found that the gene, FOXP3*, suppresses tumor growth. FOXP3 is located on the X chromosome, which means a single mutation can effectively silence the gene. This is unusual, as only one other gene linked to cancer has been found on the X chromosome.

When one copy of the FOXP3 gene is silenced, the researchers found in studying mice, 90 percent of the mice spontaneously developed cancerous tumors. The researchers also looked at FOXP3 in human breast tissue cells, comparing cancerous and non-cancerous cells. FOXP3 was found to be either deleted or mutated in a substantial portion of the cancer sample: about 80 percent of the cancer tissues studied did not express the gene at all.

In addition, the researchers found FOXP3 to be a repressor of HER-2, a protein that typically marks a more aggressive form of breast cancer. The researchers believe FOXP3 suppresses the HER-2 gene. HER-2 can be activated by many different factors, but the researchers found that when FOXP3 is normal, it keeps HER-2 levels low; when FOXP3 is missing or mutated, HER-2 levels are likely to rise.

The researchers have shown that FOXP3 was reduced or missing in about 80 percent of the more than 600 cases of breast cancer tissue examined. At this point, the researchers do not know if FOXP3 can predict breast cancer risk, like the BRCA1 and BRCA2 genes, both of which are linked to a higher risk of breast cancer.

"FOXP3 defects promote cancer development. We do not know whether this is a genetic defect that puts women at higher risk. For treatment, this gene could be quite important, but for diagnosis, it's too early to tell," says study author Yang Liu, Ph.D., deNancrede Professor of Surgery at the U-M Medical School and co-director of the cancer immunology program at the U-M Comprehensive Cancer Center. Results of the study appear in the journal Cell .

Initially, the researchers were studying FOXP3's role in autoimmune disease, when they noticed that female mice with one copy of the mutated form of the gene were developing breast cancer. Moreover, the tumors expressed high levels of ErbB2, the mouse equivalent of HER-2. Breast cancer is rare in mice, and ErbB2-positive breast cancer is even more rare.

"FOXP3 is the first X chromosome-linked gene that suppresses breast cancer and represses the HER-2/ErbB2 oncogene. Given the significant role HER-2 plays in breast cancer and the widespread defects we found on FOXP3, it is likely that this gene play an important role in suppressing breast cancer," says Pan Zheng, M.D., Ph.D., associate professor of surgery and pathology at the U-M Medical School.

The research is still in early stages. No predictive or diagnostic test is available involving this gene finding. More than 180,000 women will be diagnosed with breast cancer this year, and 40,900 will die from the disease, according to the American Cancer Society. For information about breast cancer and currently available genetic tests, visit www.mcancer.org or call the U-M Cancer AnswerLine at 800-865-1125.

In addition to Zheng and Liu, U-M study authors were Lizhong Wang, Xing Chang, Huiming Zhang, Weiquan Li, Yan Liu, Yin Wang, Bae Keun Park and Cun-Yu Wang. Additional authors are Tao Zuo, Carl Morrison, Michael W.Y. Chan, Jin-Qing Liu, Chang-gone Liu, Rulong Shen, Xingluo Liu, Tiany Yang, Tim H.-M. Huang, and Richard Love from Ohio State University; and Virginia Godfrey from the University of North Carolina, Chapel Hill.

Funding for the study was from the National Institutes of Health and U.S. Department of Defense.

The University of Michigan has filed a patent application on this research technology, and is currently looking for a corporate partner to help bring the technology to market.

http://www.med.umich.edu/

*FOXP3 is a member of the forkhead/winged-helix family of transcriptional regulators and functions as the master regulator in the development and function of regulatory T cells.

[SoCalGal]

Lani-I had a rat infestation one year before I had my recurrance, 6 years after initial (her2) BC diagnosis. I found out about the rats under my house, because I was bitten by rat mites and was terribly allergic. At the time, NO ONE else in the house had a single bite - they found me every night. It took a few visits to the dermatologist to finally figure it all out. That would be weird if that is what "triggered" my recurrance. For the record, I have another friend who had a similar problem with mites, and her and her 3 daughters were all getting bites, and Thank Gd none of them have BC.

[StephN]

Hi everyone -
we started a discussion on how the prevelance of mice and the possible ways their virus can spread at the beginning of this year. That info sure jerked my chain, so to speak.

http://her2support.org/vbulletin/showthread.php?t=26527&highlight=mice+virus

So many of us had not only indirect exposure to mice but very direct exposure.

The story continues ...

[fauxgypsy]

Around 1998-1999 I was involved in research that occasionaly used mice as subjects. Mice hate me. If anyone was bitten it was me. This doesn't include the mice I've had to dispose of when my cats brought them to me or cleaning after the occasional house mouse. I have given all of this a lot of thought simce I first heard of the MMTV. particularly since no one else in my family has a history of breast cancer that I know of.

Leslie

[fullofbeans]

When i think i was doing a good deed by saving that mouse from my cat paws..

However I think that BC is still multifactorial unlike the`MPV.

[Paris]

Having worked with horses most of my life and with many women in barns I can say that I only know of one other woman besides myself who worked in horse barns that was diagnosed with bc. I've never been in a barn that didn't have mice somewhere whether visible or not. I just don't buy this theory. There are so many women who spend countless hours working in barns and with cats and other animals. I'm just not buying this theory. Sorry gals!

Jamie

[Lani]

many risks of breast cancer are found to affect the female child of a mother exposed and there are many exposures in childhood, during puberty etc.

Mouse dropping exposure is ubiquitous. Anyone who picks something off from the floor, even a floor that has never had a mouse run over it...unless in a Japanese household... has probably been exposed to virus shed from mice which was carried in on shoes worn outdoors.

At ASCO, they showed that the incidence of breast cancer was similar with the population distribution of a certain type of rat. Other types of rats supposedly were not affected by MMTV and those other types of rats had a different geographic distribution (Asia, Australia, etc),. That is certainly not evidence of cause and effect.

Perhaps it is the combination of a genetic variation/defect in the patient combined with the MMTV infection.

Noone knows. But I would not look only for macro(large) scopic sources of mouse contamination but also for microscopic ones and much much further back than one or two decades.

When clockface painters who used radioactive paint (and licked their brushes) were found to have higher rates of cancer of the tongue and mouth, it was four or more decades later as I recall. DES exposure effects take two/three/four decades and more to manifest if I remember right.

Just food for thought