New Gene Causes Breast Cancer When Mutated

When mutated, a gene known for its ability to repair DNA appears to instead cause breast cancer.

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Dr. Nahid Mivechi,  Dr. Nita Maihle, Dr. Lan Ko, study co-authors at the Georgia Cancer Center at AU Image Source: http://bit.ly/1RqYL7u

Gene mutations are commonly known to cause a slew of diseases.

Now researchers have identified that mutations in a particular gene that is responsible for DNA repair can instead be the cause for breast and ovarian cancer.

GT198, is a co-activator of receptors for steroid hormones such as estrogen and is normally regulated by estrogen. The gene is present in all cells but most adult cells usually do not express it. In the breast, for example, it may be transiently expressed in a pregnant woman preparing for milk production and potentially in the case of breast injury. Males express it in the testes.

Researchers found the mutated version of the gene expressed both in blood and tumor tissue but the percentage was significantly higher in the tumor. They believe that once the gene is mutated it induces tumor growth.

They found the mutations in the gene at the early onset of breast and ovarian cancer. Furthermore, scientists have shown that the stem, or progenitor cells, which should ultimately make healthy breast tissue, can also have GT198 mutations that prompt them to instead make a perfect bed for breast cancer. Unfortunately, once mutated, the gene expression becomes independent on estrogen.

“This gene mutation can be in both the blood and the tumor tissue of patients, and in the tissue, it’s in high percentages,” said Dr. Lan Ko, cancer biologist in the Department of Pathology at the Medical College of Georgia at Augusta University and at the Georgia Cancer Center at AU and the study’s corresponding author. “We believe that once this gene is mutated, it induces the tumor to grow.”

The study was conducted on an international sampling from 254 cases of breast cancer in pre- and postmenopausal women.

The most interesting finding of the study is that mutated GT198 also directly affects stem cells found on blood vessels that make these various components of breast tissue. This explains why scientists have seen problems with the various components of the cancerous breast including the tissue, called the stroma, includes fat cells, or adipocytes, that provide padding; fibroblasts, which make the framework for tissue; pericytes in blood vessels, which are contractile cells that help regulate blood pressure; as well as myoepithelial cells comprising the outer layer of the ductal system through which milk flows.

“It’s a new target in cancer. It’s very exciting,” said Dr. Nita Maihle, MCG cancer biologist, associate center director for education at the university’s Cancer Center and a study co-author. “This tells you that all the different types of stromal cells in breast tissue are affected by the GT198 mutation because they all come from a common progenitor cell.”

The net effect is a tumorigenic environment filled with what Ko calls inappropriate offspring. “Here is a cause-consequence relationship,” she said.

The findings of the study have given hope for a new target for cancer therapy and treatment. The next steps would focus on finding therapies to target the misguided progenitor cells, instead of only targeting the cancerous breast tissue they produce, Ko said.

“We think the way to treat breast cancer is to target the progenitor cells. We want to kill these cells that are feeding the tumor rather than just killing the tumor cells, which is less effective.”

Read the original publication here

Source: Sciencedaily

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