Mouse virus causing mammary cancer found to infect human cells Viennese scientists show mouse breast cancer virus can infect human cells

The international research team at the Viennese Christian-Doppler-Laboratory for Gene Therapeutic Vector Development (University of Veterinary Medicine, Vienna) has shown for the first time world-wide that Mouse Mammary Tumor Virus (MMTV), which causes breast cancer in mice, can also infect human cells. The results, published in the August 1st edition of „Cancer Research -- the renowned and world-wide most frequently cited cancer journal -- has important implications. But the fact that MMTV can infect human cells, does not automatically mean that it is also involved in the development of human breast cancer. In order to confirm this causal connection scientifically, further research is still necessary", says British scientist Prof. Walter H. Günzburg, Ph.D., Head of the Christian-Doppler-Laboratory.

(PRWEB) August 4, 2005 -- The international research team at the Viennese Christian-Doppler-Laboratory for Gene Therapeutic Vector Development (University of Veterinary Medicine, Vienna) has shown for the first time world-wide that Mouse Mammary Tumor Virus (MMTV), which causes breast cancer in mice, can also infect human cells. The results, published today in the current edition of „Cancer Research -- the renowned and world-wide most frequently cited cancer journal -- has important implications. But the fact that MMTV can infect human cells, does not automatically mean that it is also involved in the development of human breast cancer. In order to confirm this causal connection scientifically, further research is still necessary", says British scientist Prof. Walter H. Günzburg, Ph.D., Head of the Christian-Doppler-Laboratory.

Scientific controversy

After a number of tantalizing yet ambiguous scientific reports stretching back to the early 70s that an MMTV like agent may be involved in human breast cancer, it was only recently that MMTV DNA could be convincingly and reproducibly shown to be present in human breast cancer specimens. Despite this intriguing finding suggestive of successful infection, other more skeptical scientists said that the presence of MMTV DNA was merely due to contamination rather than infection. Their arguments appeared to be bolstered by other studies showing that MMTV does not have the necessary key to successfully infect human cells.

Fluorescence encoding genes supply the proof

Now, the international group of scientists based in Vienna has convincingly shown that this is not the case. MMTV can actually access human cells quite efficiently and provides the hitherto missing link" said Czech born scientist Dr. Stanislav Indik, who made the discovery. For the complex experiments recombinant MMTV carrying an inserted fluorescence gene were developed. These were able to successfully infect human cells of diverse origin, e.g. breast or cervix tumor derived cells. The viruses multiplied and also infected further cells. The infected cells could be clearly seen under the microscope with the help of a fluorescent light source - proof of successful infection. The efficiency of infection of human cells was - in the best case - comparable with that obtained during infection of mouse cells, in the worst case only ten times lower. Infection requires intact MMTV envelope proteins and is blocked by heat inactivation or specific anti-viral neutralizing antibodies.

A possible role for a mouse virus in human breast cancer?

This startling finding has rekindled the discussion about a possible role for MMTV in human breast cancer. Dr. Francoise Rouault, who has spent the last eight years at the forefront of research into MMTV, explained: MMTV can be anything from an innocent passenger to a possible factor involved in the development of breast cancer, although the reality probably lies somewhere in between these two extremes." She stresses: Although some research results suggest it - it has not been shown that MMTV directly causes human breast cancer." It is however known that MMTV can cause massive holes in the immune system and this may lead to a diminished ability of the bodys natural defenses to recognize and destroy cancer cells.

An important discovery for future breast cancer- and gene therapy research

The proof that MMTV can infect human cells, opens a number of important new avenues for future research. Prof. Günzburg hopes that the further necessary financial research support will be forthcoming for the Viennese Christian-Doppler-Laboratory: The Christian Doppler Laboratory for Gene Therapeutic Vector Development is supporting much needed further studies on the effects of infection of human cells with MMTV as well as on the development of diagnostic procedures and, if a role for the involvement of the virus in cancer can be shown, its eventual treatment" said Walter H. Günzburg. Even if MMTV turns out not to cause breast cancer in humans, the data are also exciting for a completely different reason since MMTV can also be engineered as a means of efficiently delivering therapeutic genes". Indeed, this Trojan horse strategy may ironically prove particularly useful in the arsenal of weapons available for the future treatment of breast cancer.

BACKGROUND KNOWLEDGE

Retroviruses

Retroviruses of various mammals and fowl have been well known for over 70 years: One of the earliest detected retroviruses was mouse mammary tumor virus (MMTV), which, as its name implies, causes mammary tumors in mice. One of the best known viruses is human immunodeficiency virus (HIV) which was discovered in the early 1980s as the causative agent of AIDS. The necessity for the incorporation of virus genetic information (or DNA) of these viruses into the DNA of the infected cell sets these viruses apart from other viruses, as well as explains why retrovirus infections tend to last a life time and are difficult to deal with. Over the last 20 years, especially with the completion of the human genome project, it has become apparent that we humans have had a multitude of encounters with various types of retroviruses over the course of evolution. Our DNA carries the scars of these confrontations since the human genome is a graveyard for retroviruses. Indeed, latest estimates reveal that retroviruses comprise up to 10% our total genetic make-up. Nevertheless, it is thought that few if any of these retrovirus fossils can ever give rise to infectious virus.

The Christian-Doppler-Laboratory for Gene Therapeutic Vector Development

The lab, which is financed by the Christian Doppler Gesellschaft and supported by contributions from Sanochemia Pharmazeutika AG and AUSTRIANOVA Biotechnology GmbH, was established in December 2003. The laboratory has nine personnel and the aim of obtaining a better insight into the biology of retroviruses, ultimately to generate more efficient gene delivery systems that can be used for gene therapy. As well as showing infection of human cells by MMTV, the lab has demonstrated a similarity in the regulation of this virus to that of HIV, and has produced and characterized replicating gene delivery systems based upon other retroviruses like murine leukemia virus (MLV) and Rous sarcoma virus (RSV).

Sanochemia Pharmazeutika AG is a research-based pharmaceutical corporation specializing in diseases affecting the central nervous system. The companys strengths lie in developing and synthesizing active pharmaceutical ingredients to combat forms of age-related dementia, including Alzheimers disease, and to treat conditions such as Parkinsons, epilepsy and strokes.

More information: www.sanochemia.at

AUSTRIANOVA Biotechnology GmbH is a biotech company based at the University of Veterinary Medicine in Vienna specializing in the development of cell and gene based therapies for the treatment of solid tumors. Its lead product, NovaCaps®, has received orphan drug designation for pancreatic cancer in the EC.

More information: www.austrianova.com

Contact:

Walter H. Gunzburg

00431250772301

walter.guenzburg@vu-wien.ac.at

AUSTRIANOVA

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