Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human mammary epithelial cell lines with finite life span and immortal non-malignant cells - time series

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. Experiment Overall Design: We analyzed gene expression in 184 (finite life span) and HMT3522 S1 (immortal non-malignant) HMECs on successive days (3, 5, and 7) 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Katherine Martin

PROVIDER: E-GEOD-8096 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Fournier Marcia V MV Martin Katherine J KJ Kenny Paraic A PA Xhaja Kris K Bosch Irene I Yaswen Paul P Bissell Mina J MJ

Cancer research 20060701 14

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) ...[more]

PMID: 16849555

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Project description:T-cell acute lymphoblastic leukemia (T-ALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner possibly delineating specific T-ALL subgroups. One subgroup, including MLL-rearranged, CALM-AF10 or inv(7)(p15q34) cases, is characterized by elevated expression of HOXA genes. Using a gene expression based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new cases with elevated HOXA levels. Using array-CGH, a cryptic and recurrent deletion, del(9)(q34.11q34.13), was exclusively identified in 3 of these 5 cases. This deletion results in a conserved SET-NUP214 fusion product, that was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it may interact with CRM1 and DOT1L leading to the transcriptional activation of HOXA genes. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SET-NUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentiation arrest. We combined gene expression profiling and array-CGH analysis to detect a new and recurrent molecular cytogenetic abnormality in T-ALL patients that co-clustered with 5 well-defined HOXA-activated T-ALL samples. We describe the cloning of a recurrent SET-NUP214 fusion product in these samples, and identified a potential mechanism by which SET-NUP214 may activate the HOXA gene cluster as potential leukemogenic event in T-ALL. Experiment Overall Design: For 67 T-ALL patients having one of the major molecular cytogenetic abnormalities (i.e. TAL1 (n=24), LMO2 (n=9), HOXA (n=5), HOX11/TLX1 (n=7), and HOX11L2/TLX3 (n=22)), differentially expressed probesets were calculated from Affymetrix U133plus2.0 data based upon a Wilcoxon analysis and corrected for multiple testing for each probeset. Significant and differentially expressed probesets were obtained for the TAL1, HOX11 and HOX11L2 subgroups. No significant probesets were obtained for the HOXA subgroup or the LMO2 subgroup . As TAL1 and LMO2 both participate in the same transcriptional complex, activation of these genes may both lead to a highly similar expression profile. Combined analysis of TAL1 and LMO2 rearranged cases revealed significant and differentially expressed probesets that, as expected, almost entirely overlapped with the gene signature obtained for the TAL1-subgroup only. Next, we clustered 92 T-ALL cases, that besides the 67 cases as described above further included 25 T-ALL that lacked any of these recurrent abnormalities. Cluster analysis was performed based upon the top 25, 50 or 100 most significant probesets for the TAL1, TAL1/LMO2, HOX11 and HOX11L2 subgroups combined with 15 HOXA probesets identified by Soulier et al (2005)

Dataset Information

Transcription profiling of human mammary epithelial cell lines with finite life span and immortal non-malignant cells - time series

Publications

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

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