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CAMA-1MDA-MB-361 (HER2+)HCC-1569 (HER2+)BT474 (HER2+)HS578TMDA-MB-415 (Luminal)MDA-MB-231MDA-MB-468MDA-MB-436BT20TMDA-MB-157 76N10A76NF2V76NE7T47DZR75-1MCF-7MDA-MB-453.

Published byEmory Moore Modified over 8 years ago

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Presentation on theme: "CAMA-1MDA-MB-361 (HER2+)HCC-1569 (HER2+)BT474 (HER2+)HS578TMDA-MB-415 (Luminal)MDA-MB-231MDA-MB-468MDA-MB-436BT20TMDA-MB-157 76N10A76NF2V76NE7T47DZR75-1MCF-7MDA-MB-453."— Presentation transcript:

1 CAMA-1MDA-MB-361 (HER2+)HCC-1569 (HER2+)BT474 (HER2+)HS578TMDA-MB-415 (Luminal)MDA-MB-231MDA-MB-468MDA-MB-436BT20TMDA-MB-157 76N10A76NF2V76NE7T47DZR75-1MCF-7MDA-MB-453 (HER2+)HCC38M4A4NM2C5HCC-1500 HCC-1954HCC-1428HCC-1419 (HER2+)HCC-1937DU4475HCC-1806UACC-893 (HER2+)AU565 (HER2+)SKBR3 (HER2+)UACC893 (HER2+)BT483BT549 Cyclin E Actin Cyclin E Actin Cyclin E Actin Densitometry Units Subtype Immortalized ERα-positive ERα-negative LMW-E Levels A B p=0.003 Supplemental Figure 1 Immortalized ERα-positive ERα-negative Full Length Cyclin E Levels

2 ProteinFC:Senp-value I3C Sensitive Caspase 3 (active)1.73.31E-08 p531.61.77E-10 S6 pS235/pS2361.30.02 p211.30.000111 AMPK pT1721.30.00043 Smac-1.20.016 4E-BP1 pS65-1.26.38E-09 PRAS40 pT246-1.20.000488 eEF2K-1.32.52E-06 B-Raf-1.3<1.0E-15 Paxillin-1.45.97E-10 53BP1-1.41.33E-11 c.Myc-1.44.70E-08 IAP-1.53.24E-11 HER3-1.6<1.0E-15 Rb pS807/S811-1.7<1.0E-15 AIB1(SRC-1)-1.74.33E-15 AR-1.8<1.0E-15 GATA3-2.01.53E-08 PR-3.0<1.0E-15 ER alpha-6.3<1.0E-15 I3C InsensitiveFC:InSenp-value Src pY4161.30.000467 Src pY5271.32.35E-09 STAT3 pY705-1.21.00E-05 Caspase 7 cleaved D198-1.40.00317 PKC alpha-3.02.72E-10 BothFC:Senp-valueFC:InSenp-value Snail2.03.11E-121.64.63E-06 c.Jun1.43.83E-071.20.000817 Cyclin E11.42.21E-131.32.22E-12 GSK3 alpha pS21/beta pS91.37.73E-091.33.04E-13 IGF-1R beta-1.4<1.0E-15-1.4<1.0E-15 Fibronectin-1.70.000102-1.40.0166 Supplemental Table 1

3 I3C Sensitive Cellsp-value NRF2-mediated Oxidative Stress Response2.00E-10 Cell Cycle: G2/M DNA Damage Checkpoint Regulation2.14E-08 Protein Ubiquitination Pathway1.07E-07 Role of BRCA1 in DNA Damage Response3.55E-07 Molecular Mechanisms of Cancer1.20E-06 PI3K/AKT Signaling1.45E-06 Role of CHK Proteins in Cell Cycle Checkpoint Control1.78E-06 p53 Signaling2.40E-06 Actin Nucleation by ARP-WASP Complex5.75E-06 Mitotic Roles of Polo-Like Kinase1.00E-05 ATM Signaling1.00E-05 Purine Metabolism1.20E-05 Aminoacyl-tRNA Biosynthesis3.31E-05 Breast Cancer Regulation by Stathmin13.55E-05 Hereditary Breast Cancer Signaling3.63E-05 Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes3.98E-05 Apoptosis Signaling5.50E-05 Inositol Phosphate Metabolism6.03E-05 Glioma Signaling7.94E-05 Rac Signaling9.55E-05 Pancreatic Adenocarcinoma Signaling1.12E-04 Aryl Hydrocarbon Receptor Signaling1.23E-04 Induction of Apoptosis by HIV11.29E-04 Estrogen Receptor Signaling1.35E-04 Cell Cycle Control of Chromosomal Replication1.78E-04 I3C Insensitive Cellsp-value NRF2-mediated Oxidative Stress Response7.76E-07 14-3-3-mediated Signaling1.15E-05 Valine, Leucine and Isoleucine Degradation1.51E-05 Integrin Signaling2.95E-05 Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes6.03E-05 IL-8 Signaling7.76E-05 VEGF Signaling9.77E-05 One Carbon Pool by Folate1.58E-04 Virus Entry via Endocytic Pathways1.95E-04 Rac Signaling2.24E-04 Axonal Guidance Signaling2.75E-04 Actin Nucleation by ARP-WASP Complex2.82E-04 Role of Tissue Factor in Cancer3.16E-04 HER-2 Signaling in Breast Cancer3.16E-04 Actin Cytoskeleton Signaling3.47E-04 Signaling by Rho Family GTPases3.55E-04 Thrombin Signaling4.17E-04 Docosahexaenoic Acid (DHA) Signaling4.57E-04 Breast Cancer Regulation by Stathmin15.50E-04 Glioma Signaling5.50E-04 Mechanisms of Viral Exit from Host Cells6.46E-04 Cell Cycle: G2/M DNA Damage Checkpoint Regulation7.08E-04 PI3K/AKT Signaling7.41E-04 Macropinocytosis Signaling8.32E-04 Germ Cell-Sertoli Cell Junction Signaling1.07E-03 Supplemental Table 2

4 Supplemental Figure 2 IC50 (μM) Control490.8 shAHR.1585.0 shAHR.2570.0 MDA-MB-157 B Control shAHR.1 shAHR.2 Actin AhR Control sh-AHR.1 sh-AHR.2 Normalized Absorbance (590 nM) Log I3C concentration (μM) D 100 250 D 100 250 D 100 250 μM A

5 Normalized Absorbance (590 nM) Log Tamoxifen concentration (μM) A Normalized Absorbance (590 nM) Log I3C concentration (μM) B Parental TAM-R IC50 (μM) Parental0.9 TAM-R5.2 IC50 (μM) Parental277.9 TAM-R253.1 Supplemental Figure 3

6 T47D ZR75-1 MCF-7 MDA-MB-436 MDA-MB-231 MDA-MB-157 PBS DMSO 100200300400500 I3C (μM) p53 Actin - + - + - + - + I3C (250 μM) Control sh1 sh2 sh3 MCF-7 AB p53 IC50 (μM) Control265.2 shP53.1254.2 shP53.2243.8 shP53.3222.3 C MCF-7 Supplemental Figure 4 Normalized Absorbance (590 nM) Log I3C concentration (μM) Control shP53.1 shP53.2 shP53.3 p53 shRNA

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