Mouse Mammary Tumor Virus - MMTV and Human Breast Cancer

MMTV and Human Breast Cancer

As the infected mice develop mammary tumors in adulthood, MMTV has inspired the search for a human breast cancer virus. The tumors caused by MMTV in mice are benign and in general do not metastasize. Especially they do not metastasize to the bones as it is typical for human breast cancer and also for the acute leukemia caused by HTLV-I. That makes the virus not useful as a model for human breast cancer, a malignant disease.

MMTV has been found in human breast cancer. A complete proviral sequence that was greater than 95% homologous to MMTV was sequenced out of human breast cancer tissue including a correct integration into the human genome. It was named Human Mammary Tumor Virus (HMTV). There has even been a correlation to an increased prevalence of HMTV with gestational breast cancer (62% for gestational BC (=gestational breast cancer) compared with 38% for all BC) indicating that the virus may retain its hormonal regulation. Early indications of MMTV (or MMTV like) virus involvement were confused by the presence of Human Endogenous RetroVirus (HERV) sequences that have a much lower level of homology to MMTV than HMTV. These were traces of one or more viruses similar to MMTV. It is emerging that many human breast cancers contain part of the env gene of a virus that is very close to MMTV. The presence of HMTV (not HERV) sequences has been found by multiple researchers in up to 42% of breast cancers in Europe, North America as well as Australia. This is compared to only 1 to 2% of the healthy population. While some consider the presence of MMTV in humans controversial, there is a large amount of evidence that MMTV (or a very close relative) plays a role in some human breast cancers. The env gene sequences are not found in the other cells of the body suggesting that they are of foreign origin. That being said, Garry, Pogo, and Holland all have patented the use of MTV sequences for diagnostic uses in detection of human breast cancer (Pat #’s 6,670,466; 6,040,146; 5,686,247 respectively). Dr. Garry also claims that there is an endogenous version of HMTV in up to 14% of the population in his patent though he has yet to publish a peer reviewed article demonstrating his evidence.

MMTV has also been implicated in other human diseases. In the mouse, MMTV can also cause leukemia. Human breast cancer has been correlated with leukemia in humans and viral sequence has been found in these cancers. A complete proviral sequence has also been sequenced for the lymph nodes of patients with Primary Biliary Cirrhosis. Biliary epithelial cells infected with MMTV convert to the same pathology as those found in PBC patients.

MMTV is an interesting virus for human diseases. It has superantigenic properties which destroy part of the immune system of the infected mouse. The well documented MMTV pathogenesis helps to understand the action of superantigens in human disease.

In the last few years a number of labs have found MMTV like DNA in human breast cancer tissue and most recently, the virus has been shown to be able to productively infect human cells, possibly suggesting that an MMTV like virus may play a role in human breast cancer. It was shown too, that human breast cancer often occurs in areas where Mus domesticus is the prominent species of mice. In the lab, MMTV was shown to readily infect canine and feline tissue culture cells.One theory of how MMTV would be passed to humans is through contact with our pets. Although it is difficult to imagine how modern women would get infected by a mouse virus, an infection of both species by the same food might be a possibility, or passage from one species to the other may also occur.This mode of infection might explain the often seen development of benign or malignant mammary tumors in pets.Dogs and cats are often affected and they too have access to human food and share living space with humans.