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Cellular and Molecular Targets of Estrogen in Normal Human Breast Tissue¹

Departments of Adult Oncology [P. S., D. P., J. L-D., K. P.] and Cancer Biology [Y. G.], Dana-Farber Cancer Institute; Department of Pathology, Brigham and Women’s Hospital [A. R.]; and Departments of Medicine [P. S., D. P., K. P.] and Pathology [Y. G., A. R.], Harvard Medical School, Boston, Massachusetts 02115

To gain insight into the in vivo role of estrogen, we isolated estrogen receptor-positive cells fromnormal human breast tissue using a recombinant adenovirus that expresses green fluorescence protein in response to estrogen. We compared the global gene expression profile of these estrogen receptor-positive cells with that of various normal and cancerous mammary epithelial cells and identified several genes not implicated previously in estrogen signaling. One of these genes, lipocalin 2, is a putative in vivo estrogen target gene and paracrine factor that mediates the growth regulatory effects of estrogen in normal breast epithelium. These results demonstrate that normal and cancerous estrogen receptor-positive cells are distinct at the molecular level and suggest that lipocalin 2 is a new therapeutic target for breast cancer prevention and treatment.

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