Human Gene Set: RIZKI_TUMOR_INVASIVENESS_3D_DN


Standard name RIZKI_TUMOR_INVASIVENESS_3D_DN
Systematic name M11472
Brief description Genes down-regulated in three-dimentional (3D) cultures of preinvasive (S3-C) vs invasive (T4-2) breast cancer cells.
Full description or abstract A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from preinvasive to invasive phenotype as it may occur spontaneously in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted basement membrane cultures. These cells remained noninvasive; however, unlike their nonmalignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher-grade tumors. To find functionally significant changes in transition from preinvasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between preinvasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP9, MMP13, MMP15, and MMP17 was up-regulated in the invasive cells. Using small interfering RNA-based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which preinvasive breast cells could acquire invasiveness in a metaplastic context.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18316601   Authors: Rizki A,Weaver VM,Lee SY,Rozenberg GI,Chin K,Myers CA,Bascom JL,Mott JD,Semeiks JR,Grate LR,Mian IS,Borowsky AD,Jensen RA,Idowu MO,Chen F,Chen DJ,Petersen OW,Gray JW,Bissell MJ
Exact source File 3S: S3C vs. T4 in 3D
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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