Augusta University Researchers Study Gene that Could be Better Target in Breast Cancer
A gene that appears to be active very early in breast cancer could provide an important clue to how it begins and provide a better target for drugs to prevent it, said researchers at the Cancer Center at Augusta University.
Augusta University cancer researchers Dr. Nita Maihle and Dr. Lan Ko have published a study on a gene that appears to be active in early breast cancer. The gene is in the same area as the breast cancer risk gene BRCA1.
In a study published today in the American Journal of Pathology, the researchers focus on gene GT198, a gene known to be involved in DNA repair and hormone receptor activation. It is from the same general area on chromosome 17 as the more famous breast cancer risk gene BRCA1. But once that gene was first identified and published in 1994, “then the field moved on to study BRCA1 function,” said Dr. Lan Ko, a cancer biologist at AU. “People no longer focused on this (area.)”
The problem with BRCA1 is its mutation can be found in families at greater risk of breast cancer, Ko said. “But when you really go down to the tumor tissue, most of them, which is called sporadic cancer, they don’t have the mutation of BRCA1,” she said. “Then how sporadic cancer is started becomes a problem.”
The AU researchers think they have found the answer in GT198 by looking in the supporting tissue known as the stroma. Those cells stimulate normal breast tissue to grow. Most researchers have focused their attention on the tumors themselves but “Lan has figured out there are cancer-causing mutations in the” supporting cells, said co-author Dr. Nita J. Maihle. “That’s a huge thing.”
The mutation appears to hijack the normal support system once those cells are mutated, Ko said.
“The stimulation signal is no longer normal, it is too much,” and begins pushing those normal cells toward creating a tumor, she said. “This is like a small scale evolution. The tumor cells actually keep dying but they have a force to keep pushing behind them so they keep growing.”
Unlike some other cancer-causing mutations, the GT198 is only found in hormone-sensitive organs like the breast, which can explain how it can take over that normally hormone-driven system, Ko said.“Once this group gets mutated, the consequence is (like having) too much hormone,” she said. “They will keep stimulating even without hormone.”
It is an “estrogen-like effect,” Maihle said. That could explain why breast cancer can arise in post-menopausal women, Ko said.
Those women aren’t producing a lot of hormones but “it is actually mutation causing this effect,” she said.
The researchers are now looking at whether there are drugs or other substances that could inhibit GT198 but they believe they have found an important early signal for what will develop into breast cancer.
“We will have a marker to tell where the breast cancer starts from the beginning,” Ko said. “And then we plan to generate inhibitors against those cells so that we can prevent cancer from the beginning.”
“In its earliest stages,” Maihle said.
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