Supplementary Materials

The PDF file includes:

  • Fig. S1. HIF-1α is not appreciably stabilized in 3D culture.
  • Fig. S2. Abundance of the heterogeneously regulated gene cluster is perturbed by NRF2 knockdown or p53 disruption, but not by JUND knockdown or human papillomavirus E7–induced inhibition of RB.
  • Fig. S3. NRF2 knockdown and 3D phenotype quantification in MCF10A-5E cells.
  • Fig. S4. Proliferation differences and signaling similarities between MCF10A-5E and MCF10DCIS.com cells.
  • Fig. S5. NRF2 knockdown causes p53 stabilization in premalignant breast epithelial cell lines.
  • Fig. S6. Premalignant breast epithelial cell lines have similar adaptations to NRF2 knockdown in spheroid culture.
  • Fig. S7. Representative immunoblot images for the double-strand break and oxidative stress time courses in MCF10A-5E cells.
  • Fig. S8. Local niches of NRF2 stabilization in MCF10A-5E 3D spheroids and pubertal murine mammary glands.
  • Fig. S9. Description and validation of the HyPer-2 probe for H2O2 and the mRFP1-NRF2 reporter.
  • Fig. S10. Antioxidant treatment causes an overall increase in MCF10A-5E spheroid size.
  • Fig. S11. Oxidative stress stabilizes NRF2 in the cytoplasm more so than electrophilic stress.
  • Fig. S12. Oxidative stress does not measurably inhibit MDM2 induction by stabilized p53.
  • Fig. S13. NRF2 perturbations do not detectably alter MDM2 abundance.
  • Fig. S14. Calibration of an integrated NRF2-p53 systems model for oxidative stress.
  • Fig. S15. Endogenous NRF2 and p21 are not proximity labeled by BirA* fusions of each other.
  • Fig. S16. Anti-NRF2 antibody validation for immunohistochemistry.
  • Fig. S17. NRF2 and p53 are costabilized in breast epithelial ducts.
  • Fig. S18. Low-magnification hematoxylin-eosin images of the tissues and tumors in the work.
  • Table S1. qPCR primer sequences.
  • Table S2. Parameter summary for the integrated NRF2-p53 computational model.
  • Legends for data files S1 to S4
  • References (136151)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (Microsoft Excel format). Promoter analysis results underlying the summary Venn diagram in Fig. 1B.
  • Data file S2 (Microsoft Excel format). GO enrichment analysis.
  • Data file S3 (Microsoft Excel format). Gene set enrichment analysis of differentially abundant transcripts in MCF10A-5E and MCF10DCIS.com cells upon NRF2 knockdown compared with control.
  • Data file S4 (.zip format). NRF2-p53 computational model and associated files.