Researchers have revealed that a protein involved in the growth of some forms of leukemia has now been found to play a mixed role in breast cancer development.
Experts from the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC) say that this finding indicates that the function of the protein, known as Stat5a, may be different in developing breast cancer cells that are estrogen receptor-positive as compared to estrogen receptor-negative.
AdvertisementPresenting their findings at the annual meeting of the Endocrine Society in Washington, DC, the researchers revealed that when estrogen receptor levels were over-expressed, loss of Stat5a reduced development of a lobular type of preneoplasia.
However, when estrogen receptor levels were normal, loss of Stat5a not only had no effect on reducing preneoplasia, but also increased susceptibility to carcinogen-induced breast cancer.
According to the researchers, the new findings illustrate the importance of breast cancer heterogeneity when testing new therapeutic targets.
The researchers agree that Stat5a could be a target for treatment of leukemia.
However, lead author Dr. Anne Miermont, a doctoral graduate student in tumor biology at Georgetown University Medical Center, adds: "If Stat5a is to be used as a drug target for leukemia or other cancers, it is important to fully understand how altering its function impacts the breast, especially since it appears it may play different roles in different types of breast cancer."
Stat5a belongs to a family of proteins that are key to regulating cell growth and differentiation. Because they have been found to be over-expressed in leukemia, the researchers sought to see whether they were important in breast cancer development or not.
Miermont and Dr. Priscilla Furth, a professor of oncology, say that estrogen receptors are over-expressed in more than half of human breast cancers, and thus they set up studies to test whether the function of Stat5a was the same or different in cells with estrogen receptor over-expression or not.
Their study showed that Stat5a A is rather "two-faced" when it comes to its role in breast tissue.
Miermont found that when the animals were exposed to a cancer-causing chemical, they were more likely to develop breast cancer than mice with intact Stat5a genes.
However, when estrogen receptor was over-expressed, Stat5a collaborated with it to promote growth of a type of pre-cancerous lesion of the breast termed a hyperplastic alveolar nodule.
"Our studies in in vivo mouse models illustrate a dual role for the Stat5a protein in breast tissue. While it can contribute to the growth of one type of precancerous lesion in the breast, this protein also appears to protects mammary cells from carcinogenic exposure," says Miermont.
Furth says that these findings need to be validated and expanded, but she adds that while Stat5a is obviously a complicated protein that has many functions, the results underscore the need to specifically understand the mechanisms that regulate its different roles in breast cells and how changes in Stat5a activity may affect different types of breast cancer generation.
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