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Systematic drug perturbations of cancer cells reveal diverse exit paths from the proliferative state

ABSTRACT: Analysis of the time courses of gene expression profiles of breast cancer cell line MCF7 treated by 16 differentiation-inducing drugs at day 1, day 3 and day 5. The drugs are the screening results from the the JHCCL library (1,500 drugs). The hypothesis tested in the present study was that cancer cells exit the proliferative state via multiple paths. Results showed that cell state transition trajectories firstly diverged and later converged to a quiescient differentiated state

ORGANISM(S): Homo sapiens

PROVIDER: GSE74281 | GEO | 2015/10/23

SECONDARY ACCESSION(S): PRJNA299623

REPOSITORIES: GEO

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Project description:Cells must adjust their gene expression in order to compete in a constantly changing environment. Two alternative strategies could in principle ensure optimal coordination of gene expression with physiological requirement. First, the internal physiological state itself could feedback to regulated gene expression. Second, the expected physiological state could be inferred from the external environment, using evolutionary-tuned signaling pathways. Coordination of ribosomal biogenesis with the requirement for protein synthesis appears to be particularly important, since cells devote a large fraction of their biosynthetic capacity for ribosomal biogenesis. To define the relative importance of internal vs. external sensing to the regulation of ribosomal biogenesis gene expression, we subjected S. cerevisiae cells to conditions which decoupled the actual vs. environmentally-expected growth rate. Gene expression followed the environmental signal according to the expected, but not the actual, growth rate. Simultaneous monitoring of gene expression and growth rate in chemostat-grown cultures further confirmed that ribosome biogenesis genes responded rapidly to changes in the environments but were oblivious to longer-term changes in growth rate. Our results suggest that the capacity to anticipate and prepare for environmental changes presented a major selection force during yeast evolution. Keywords: Saccharomyces_Cerevisiae, Stress response, ADH1 deletion, time courses, chemostat Experiment 1: ADH1 deletion cells, which grow faster on glycerol rather then glucose medium, were grown in both glucose and glycerol medium. The cells expression on glycerol is compared to their expression glucose (5 microarrays). Experiment 2: Time course of ADH1 deletion cells upon growth on glycerol and on glucose (7 microarrays). Experiment 3: Response of steady state grown cells to environmental perturbations. Cells were grown in glucose or histidine limited chemostats and reached steady state. The cells were then subjected to perturbations such as DTT, heat shock, NaCl, Clotrimazole, H2O2, and addition of limiting factors (histidine and glucose, respectively). Overall we have examined 10 timecourses with 83 microarrays.

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Systematic drug perturbations of cancer cells reveal diverse exit paths from the proliferative state

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