p53 deficiency linked to B cell translocation gene 2 (BTG2) loss enhances metastatic potential by promoting tumor growth in primary and metastatic sites in patient-derived xenograft (PDX) models of triple-negative breast cancer

Breast Cancer Research : BCR
Emily PowellHelen Piwnica-Worms

Abstract

Despite advances in early diagnosis and treatment of cancer patients, metastasis remains the major cause of mortality. TP53 is one of the most frequently mutated genes in human cancer, and these alterations can occur during the early stages of oncogenesis or as later events as tumors progress to more aggressive forms. Previous studies have suggested that p53 plays a role in cellular pathways that govern metastasis. To investigate how p53 deficiency contributes to late-stage tumor growth and metastasis, we developed paired isogenic patient-derived xenograft (PDX) models of triple-negative breast cancer (TNBC) differing only in p53 status for longitudinal analysis. Patient-derived isogenic human tumor lines differing only in p53 status were implanted into mouse mammary glands. Tumor growth and metastasis were monitored with bioluminescence imaging, and circulating tumor cells (CTCs) were quantified by flow cytometry. RNA-Seq was performed on p53-deficient and p53 wild-type tumors, and functional validation of a lead candidate gene was performed in vivo. Isogenic p53 wild-type and p53-deficient tumors metastasized out of mammary glands and colonized distant sites with similar frequency. However, p53-deficient tumors metastasized e...Continue Reading

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Citations

Mar 6, 2017·Clinical & Experimental Metastasis·Katherine BankaitisJosh Neman
Apr 17, 2019·Journal of the National Cancer Institute·Utpal K MukhopadhyayGokul M Das
May 14, 2017·Journal of Hematology & Oncology·Yunxin LaiPeng Li
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Mar 30, 2021·Frontiers in Oncology·Kevin Roarty, Gloria V Echeverria

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Datasets Mentioned

BETA
GSE76433

Methods Mentioned

BETA
xenograft
flow cytometry
transfection
RNA-Seq
flow cytometery
bioluminescence imaging
blood draw

Software Mentioned

GeneGo
MetaCore
Tophat2
Partek Genomics Suite
Living Image
R
DESeq2

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