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The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor

ABSTRACT: The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor

PROVIDER: PRJNA484727 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7647600_1.fastq.gz	Fastqsanger.gz
	SRR7647600_2.fastq.gz	Fastqsanger.gz
	SRR7647610_1.fastq.gz	Fastqsanger.gz
	SRR7647610_2.fastq.gz	Fastqsanger.gz
	SRR7647620_1.fastq.gz	Fastqsanger.gz

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The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent CGH)

Project description:The Wnt gene family is an evolutionarily conserved group of proteins that regulate cell growth, differentiation, and stem cell self-renewal. Aberrant Wnt signaling in human breast tumors has been proposed to be an attractive drug target, especially in the basal-like subtype where canonical Wnt signaling is both enriched and predictive of poor clinical outcomes. The development of effective Wnt based therapeutics, however, has been slowed in part by a limited understanding of the context dependent nature with which these aberrations influence breast tumorigenesis. We recently reported that MMTV-Wnt1 mice, which are an established model for studying Wnt signaling in breast tumors, develop two subtypes of tumors by gene expression classification: Wnt1-EarlyEx and Wnt1-LateEx. Here, we extend this initial observation and show that Wnt1-EarlyEx tumors had high expression of canonical Wnt, non-canonical Wnt, and EGFR signaling pathway signatures. Therapeutically, Wnt1-EarlyEx tumors had a dynamic reduction in tumor volume when treated with an EGFR inhibitor. Wnt1-EarlyEx tumors also had primarily Cd49fpos/Epcamneg FACS profiles, but were unable to be serially transplanted into wild-type FVB female mice. Wnt1-LateEx tumors, conversely, had a bloody gross pathology, which was highlighted by the presence of ‘blood lakes’ by H&E staining. These tumors had primarily Cd49fpos/Epcampos FACS profiles, but also contained a secondary Cd49fpos/Epcamneg subpopulation. Wnt1-LateEx tumors were enriched for activating Hras1 mutations and were capable of reproducing tumors when serially transplanted into wild-type FVB female mice. This study definitely shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors. Importantly, these subtypes differ in their therapeutic response to an EGFR inhibitor, suggesting that a subset of human tumors with aberrant Wnt signaling may also respond to erlotinib.

2019-06-26 | GSE118161 | GEO

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (RNA-seq)

2019-06-26 | GSE118163 | GEO

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent gene expression)

2019-06-26 | GSE118162 | GEO

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (RNA-seq)

Project description:The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (RNA-seq)

| PRJNA484731 | ENA

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent CGH)

Project description:The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent CGH)

| PRJNA484732 | ENA

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent gene expression)

Project description:The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor (Agilent gene expression)

| PRJNA484733 | ENA

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor.

Project description:The Wnt gene family encodes an evolutionarily conserved group of proteins that regulate cell growth, differentiation and stem cell self-renewal. Aberrant Wnt signaling in human breast tumors has been proposed as a driver of tumorigenesis, especially in the basal-like tumor subtype where canonical Wnt signaling is both enriched and predictive of poor clinical outcomes. The development of effective Wnt-based therapeutics, however, has been slowed in part by a limited understanding of the context-dependent nature with which these aberrations influence breast tumorigenesis. We previously reported that MMTV-Wnt1 mice, an established model for studying Wnt signaling in breast tumors, develop two subtypes of tumors by gene expression classification: Wnt1-EarlyEx and Wnt1-LateEx Here, we extend this initial observation and show that Wnt1-EarlyEx tumors exhibit high expression of canonical Wnt, non-canonical Wnt, and EGFR signaling pathway signatures. Therapeutically, Wnt1-EarlyEx tumors showed a dynamic reduction in tumor volume when treated with an EGFR inhibitor. Wnt1-EarlyEx tumors had primarily Cd49fpos/Epcamneg FACS profiles, but it was not possible to serially transplant these tumors into wild-type FVB female mice. Conversely, Wnt1-LateEx tumors had a bloody gross pathology, which was highlighted by the presence of 'blood lakes' identified by H&E staining. These tumors had primarily Cd49fpos/Epcampos FACS profiles, but also contained a secondary Cd49fpos/Epcamneg subpopulation. Wnt1-LateEx tumors were enriched for activating Hras1 mutations and were capable of reproducing tumors when serially transplanted into wild-type FVB female mice. This study definitively shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors that differ in multiple biological aspects including sensitivity to an EGFR inhibitor.

| S-EPMC6679375 | biostudies-literature

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-06-26 | GSE118164 | GEO

Gene expression profiling using RNA-Seq data of MMTV-Wnt1 tumor tissue from mice treated with E7386

Project description:We conducted an RNA-Seq analysis using total RNA extracted from MMTV-Wnt1 tumor tissues resected from mice orally administered E7386 at 25 or 50 mg/kg twice daily, or vehicle, for 3 days (Day 4) or 7 days (Day 8) and examined the differentially expressed gene levels compared with vehicle at days 4 and 8.

2020-12-21 | GSE158713 | GEO

Whole-genome expression profiling of metastatic versus non-metastatic mammary tumors in MMTV-Wnt1 transgenic mice

Project description:To identify genes that mediate lung metastasis in breast cancer, we compared expression profiles of metastatic versus non-metastatic mammary tumors in MMTV-Wnt1 transgenic mice. A subset of biologically relevant genes with statistically significant changes was selected for validation. These genes include Alox15, Ptn, Ror2, Sox9, Jag2 and Runx2. These genes encode proteins that play important roles in the immune and inflammatory responses as well as osteogenesis and skeletal morphogenesis.

2019-07-26 | GSE84917 | GEO

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