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Gene Expression Signature in Organized and Growth-Arrested Mammary Acini Predicts Good Outcome in Breast Cancer

¹ Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California and ² Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, Massachusetts

Requests for reprints: Mina J. Bissell, Life Sciences Division, Department of Cancer Biology, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720. Phone: 510-486-4365; Fax: 510-486-5586; E-mail: mjbissell{at}lbl.gov.

Nonmalignant human mammary epithelial cells (HMEC) seeded in laminin-rich extracellular matrix (lrECM) form polarized acini and, in doing so, transit from a disorganized proliferating state to an organized growth-arrested state. We hypothesized that the gene expression pattern of organized and growth-arrested HMECs would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in 184 (finite life span) and HMT3522 S1 (immortal nonmalignant) HMECs on successive days after seeding in a lrECM assay. Both HMECs underwent growth arrest in G₀-G₁ and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines and examined the expression of these genes in a previously published panel of microarray data for 295 breast cancer samples. We show that genes that are significantly lower in the organized, growth-arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically. (Cancer Res 2006; 66(14): 7095-102)

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