| Autor: |
Hanna, Ann, Nixon, Mellissa J., Estrada, M. Valeria, Sanchez, Violeta, Sheng, Quanhu, Opalenik, Susan R., Toren, Abigail L., Bauer, Joshua, Owens, Phillip, Mason, Frank M., Cook, Rebecca S., Sanders, Melinda E., Arteaga, Carlos L., Balko, Justin M. |
| Rok vydání: |
2022 |
| DOI: |
10.6084/m9.figshare.20335398 |
| Popis: |
Additional file 1. Fig 1: Dusp4 hemi- or homozygous deletion does not accelerate MMTV-neu-mediated tumorigenesis or growth. A) Kaplan–Meier survival of FVB/n NIC mice with Dusp4WT (n=8), Dusp4FLOX/WT (n=11), or Dusp4FLOX (n=10) alleles. Time from birth to tumor endpoint (2cm3 total tumor burden), time from birth to first palpable tumor, and time from palpable tumor to tumor endpoint are shown. B) Dusp4 mRNA expression measured from bulk tumor RNA from mice in (A). C) Representative western blot analysis of bulk tumor lysates (n=4 per group) from tumors in (A). Fig 2: Co-occurrence of TP53 mutations, DUSP4 loss, and MYC amplification in primary breast cancer. A) TCGA (Firehose legacy) analysis of the co-occurrence of TP53 mutations, DUSP4 loss, and MYC amplification, accessed from the cBioPortal Web site. B) Schema for generation of a series of cell lines derived from Dusp4FLOX PMECs carrying deletion/excision of Dusp4, deleterious p53 mutations, and MYC overexpression/amplification. Fig 3: Characterization of the primary mammary epithelial cells generated from Dusp4FLOX cell line. Dusp4 functional loss of exons 3-4 (encoding the phosphatase in PMEC cells was confirmed by A) NGS and B) qRT-PCR analysis. C) Summary of all Trp53 mutations as assessed by NGS in cell lines derived from Dusp4FLOX PMECs. D) Validation of Trp53 deletion in PMEC cell lines by immunoblotting. Fig 4: Low-pass WGS copy number analysis example. Log2 reads from low-pass WGS organized by genomic location. Dusp4NULL Trp53Δex7 MYCAMP demonstrate a focal amplification event (red box) including the centromeric portion of 5q, likely including the centromere. Dusp4FLOX cells are included as a visual control. Fig 5: Elevated mRNA expression of key genes included on the 5q amplification associated with tumorigenic potential. A) UCSC Genome browser snapshot identifying key genes included in the 5q amplification event associated with tumorigenic potential. B) mRNA expression level for key genes from (A) measured by qRT-PCR in derivative PMEC cell lines. Tu: tumorigenic potential. Fig 6: Dusp4 deletion suppresses the cellular proliferation without impacting survival of PMEC cell lines. A) Time-course assessment of the proliferative capacity of Dusp4-derived PMEC cell lines by sulforhodamine B (SRB) assay. B) Dose–response assessment of survival in Dusp4-derived PMEC cell line treated with Palbociclib by SRB assay. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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