Research in Leena Hilakivi-Clarke's Laboratory

Research

We study whether timing of exposure to dietary components that alter circulating estrogen levels or interact with the estrogen receptor determines their effect on breast cancer risk. Results obtained by us and other investigators indicate that the sensitivity of the mammary gland to estrogens varies, depending on the time period when the exposure occurs. Periods of increased sensitivity include pregnancy and menarche, when the breast undergoes extensive proliferation and differentiation, partly due to being exposed to high estrogen levels. 

High in utero estrogen levels alter normal programming of the mammary gland, and result an increase in the number of targets for malignant transformation, increased mammary epithelial density and changes in the expression of estrogen-regulated genes, including the estrogen receptor (ER) alpha, beta and protein kinase C. Increased in utero estrogen levels increase later breast cancer risk. 

If estrogen levels are elevated around puberty, mammary gland undergoes early differentiation, resulting elimination of targets for malignant transformation. We have also found that prepubertal estrogen exposure reduces the expression of ER alpha, and increases the expression of ER beta and BRCA1. Further, prepubertal estrogen exposure reduces later risk of developing mammary tumors. Findings of other investigators showing that early pregnancy or an exposure to pregnancy-mimicking estrogen levels reduces breast cancer risk, support the view that estrogens can reduce the risk of developing this disease, if exposed shortly before or after puberty.