Posted October 14, 2014
Yi Li, Baylor College of Medicine
Epidemiological studies have shown that a pregnancy before age 22 lowers a woman's risk of breast cancer, while pregnancies that begin after age 35 increase breast cancer risk. It is unclear what pregnancy-associated changes can increase cancer risk. Supported by BCRP funding, Dr. Li identified a key protein that, during pregnancy, allows pre-cancerous cells to evade the body's natural defenses that normally keep cell proliferation in check. With BCRP funding early in his career, Dr. Li developed a novel mouse model that closely mimics breast cancer initiation in humans. Using this model, he tested the hypothesis that first pregnancies impart different effects on breast cancer risk due to divergent amounts of mutations in the breast cells in younger versus older women. Dr. Li found that the transcription factor, STAT5, contributed to tumorigenesis in pregnant mice through the suppression of apoptosis in early breast lesion cells, thereby increasing their tendency to become cancerous. Dr. Li's most recent findings, published in eLIFE, have shown that active STAT5 is detectable in human breast lesions, especially in women who have had a pregnancy. Interestingly, the remodeling of breast tissue during pregnancy - specifically, changes in expression levels of lactation hormones - stimulates STAT5 and consequently weakens the cellular mechanisms that kill off precancerous cells by apoptosis. Based on these findings, STAT5 could represent a potential target to prevent and/or reduce the risk of breast cancer in pregnant women over the age of thirty-five. Dr. Li is partnering with industry to conduct a clinical trial to test a STAT5 inhibitor in pre- and post-menopausal women. Dr. Li commented, "I am extremely grateful to the DoD BCRP for its generous support of my research program at Baylor as well as my postdoctoral research training. This support has allowed me to explore some very risky research ideas. I am gratified that some of these ideas have generated potential clinical significance, and we are excited to now be moving toward a clinical trial."
Haricharan S, Dong J, Hein S, Reddy JP, Du Z, Toneff M, Holloway K, Hilsenbeck SG, Huang S, Atkinson R, Woodward W, Jindal S, Borges VF, Gutierrez C, Zhang H, Schedin PJ, Osborne CK, Tweardy DJ, Li Y. Mechanism and preclinical prevention of increased breast cancer risk caused by pregnancy. eLIFE. 2013 Dec 31;2:e00996.
Public and Technical Abstracts: STAT5 as a Molecular Target for Breast Cancer Prevention