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. Author manuscript; available in PMC: 2014 Jun 16.
Published in final edited form as: Science. 2011 Dec 8;335(6066):348–353. doi: 10.1126/science.1212728

Figure 4. The E1 SUMO-activating enzyme is required to support MYC-dependent human breast cancers.

Figure 4

a) Myc-dependency in breast cancer cells. Breast cancer-derived cell lines infected with control-or Myc-shRNA lentivirus were analyzed for clonogenic growth. Macroscopic colonies were quantified and normalized to control-shRNA infected cells for each cell line.

b) Inactivation of SAE2 inhibits clonogenicity in Myc-dependent breast cancer cells. Breast cancer-derived cell lines infected with dox-inducible control-or SAE2 -shRNA lentivirus were analyzed for clonogenic growth +/− dox.

c) Inactivation of SAE2 inhibits tumorigenicity of Myc-dependent tumors. Myc-dependent (SUM159 and MDA-MB-231, left and middle panels, respectively) or Myc-independent (MCF7, right panel) breast cancer cells infected with dox-inducible SAE2-targeting shRNA lentivirus were transplanted into nude mice. Recipient animals were treated +/− dox and xenograft volume was measured over time.

d) Low SUMO-Activating-Enzyme expression correlates with patient metastasis-free survival selectively in Myc-high breast cancers. The expression of SAE1/SAE2 is inversely correlated with increased metastasis-free survival in patients with Myc-high tumors (p=0.001, log-rank test). Tumors with the highest and lowest tertile of Myc mRNA expression were considered “Myc high” and “Myc low,” respectively. Patients with the highest-and lowest -tertile of SAE1/SAE2 mRNA expression are shown as blue and red lines, respectively.