Systematic name M10395
Brief description Genes up-regulated in non-spontaneously immortalizing (NSI) primary breast cancer tumor cultures upon expression of TERT [GeneID=7015] off a retroviral vector.
Full description or abstract An improved understanding of cell immortalization and its manifestation in clinical tumors could facilitate novel therapeutic approaches. However, only rare tumor cells, which maintain telomerase expression in vitro, immortalize spontaneously. By expression-profiling analyses of limited-life primary breast tumor cultures pre- and post-hTERT transduction, and spontaneously immortalized breast cancer cell lines, we identified a common signature characteristic of tumor cell immortalization. A predominant feature of this immortalization signature (ImmSig) was the significant overexpression of oxidoreductase genes. In contrast to epithelial cells derived from low histologic grade primary tumors, which required hTERT transduction for the acquisition of ImmSig, spontaneously immortalizing high-grade tumor cultures displayed similar molecular changes independent of exogenous hTERT. Silencing the hTERT gene reversed ImmSig expression, increased cellular reactive oxygen species levels, altered mitochondrial membrane potential and induced apoptotic and proliferation changes in immortalized cells. In clinical breast cancer samples, cell-proliferation-pathway genes were significantly associated with ImmSig. In these cases, ImmSig expression itself was inversely correlated with patient survival (P=0), and was particularly relevant to the outcome of estrogen receptor-positive tumors. Our data support the notion that ImmSig assists in surmounting normal barriers related to oxidative and replicative stress response. Targeting a subset of aggressive breast cancers by reversing ImmSig components could be a practical therapeutic strategy.
Collection ARCHIVED: Archived Founder gene sets that are referenced by current Hallmarks
      C2_NONE: ARCHIVED Curated
            C2_CGP: ARCHIVED Chemical and Genetic Perturbations
Source publication Pubmed 17471242   Authors: Dairkee SH,Nicolau M,Sayeed A,Champion S,Ji Y,Moore DH,Yong B,Meng Z,Jeffrey SS
Exact source Suppl. Data 2: red
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.0: First introduced

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