Gene expression signature in organized and growth arrested mammaryacini predicts good outcome in breast cancer
To understand how non-malignant human mammary epithelial cells (HMEC) transit from a disorganized proliferating to an organized growth arrested state, and to relate this process to the changes that occur in breast cancer, we studied gene expression changes in non-malignant HMEC grown in three-dimensional cultures, and in a previously published panel of microarray data for 295 breast cancer samples. We hypothesized that the gene expression pattern of organized and growth arrested mammary acini would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in two HMEC cell lines, 184 (finite life span) and HMT3522 S1 (immortal non-malignant), on successive days post-seeding in a laminin-rich extracellular matrix 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. 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.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of Biological andEnvironmental Research; National Cancer Institute 2 R01 CA064786-09,Department of Defense. Breast Cancer Research Program BC012005 and BCRPDAMD17-00-1-0224, National Institutes of Health. National Institute ofAllergy and Infectious Diseases U19-AI057319
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 888776
- Report Number(s):
- LBNL-59796; CNREA8; R&D Project: 443180; BnR: KP1104010; TRN: US200623%%549
- Journal Information:
- Cancer Research, Vol. 66, Issue 14; Related Information: Journal Publication Date: 07/15/2006; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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