Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer.
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.
Fournier
Marcia V
MV
Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Martin
Katherine J
KJ
Kenny
Paraic A
PA
Xhaja
Kris
K
Bosch
Irene
I
Yaswen
Paul
P
Bissell
Mina J
MJ
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis