Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer

Marcia V. Fournier, Katherine J. Martin, Paraic A. Kenny, Kris Xhaja, Irene Bosch, Paul Yaswen, Mina J. Bissell

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90 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7095-7102
Number of pages8
JournalCancer Research
Volume66
Issue number14
DOIs
StatePublished - Jul 15 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fournier, M. V., Martin, K. J., Kenny, P. A., Xhaja, K., Bosch, I., Yaswen, P., & Bissell, M. J. (2006). Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Research, 66(14), 7095-7102. https://doi.org/10.1158/0008-5472.CAN-06-0515