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Mus musculus

ABSTRACT: RNA-seq of MMTV-Neu AXL KO tumors

PROVIDER: PRJNA397625 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5909446_1.fastq.gz	Fastqsanger.gz
	SRR5909446_2.fastq.gz	Fastqsanger.gz
	SRR5909447_1.fastq.gz	Fastqsanger.gz
	SRR5909447_2.fastq.gz	Fastqsanger.gz
	SRR5909448_1.fastq.gz	Fastqsanger.gz

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DIMETHYLBENZANTHRACENE (DMBA) INDUCED MAMMARY CARCINOGENESIS IN MMTV-Neu and MMTV/p53 KO FEMALE MICE AND EFFECTS OF REXINOIDS

Project description:Murine models of mammary cancers have proven to be highly informative on numerous fronts including individual gene causation, microenvironmental analyses, and chemoprevention studies. The MMTV-Neu transgenic model of mammary cancer has proven to be a useful model and has been employed in several prevention studies. However, there are certain practical drawbacks to its use including long tumor latencies and a tendency to develop mutations in the transmembrane domain of Neu (unlike human HER2/Neu overexpressing breast cancers). Here we report modifications that were made in an attempt to optimize this mouse model for chemopreventive screening. First, homozygous MMTV-Neu and homozygous P53 KO mice were crossed to create a MMTV-Neu/P53+/- strain (which more closely approximates the genetic make-up of most HER2+ human patients). Second, to overcome the drawback of long tumor latencies, the mice were treated with DMBA for eight weeks. DMBA treatment greatly decreased the latency of mammary carcinomas in the MMTV-Neu mice although the resulting tumors remained histopathologically similar to those from MMTV-Neu control mice. Next, we examined gene expression in tumors derived from MMTV-Neu, MMTV-Neu/p53+/-, and DMBA treated mice. It was found that the characteristic MMTV-Neu tumor-defined expression pattern was still the most prevalent feature of all the MMTV-Neu tumors despite their being crossed to the p53 null allele, treated with DMBA, or both. However, tumors from the DMBA treated animals exhibited many unique gene expression changes including the high expression of stress response, defense, and inflammation genes. Finally, we demonstrated that the RXR agonists UAB30 and Targretin, both inhibited mammary cancer formation in MMTV-Neu mice, including those treated with DMBA. These results demonstrate the potential utility of this murine model for additional chemoprevention studies.

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RNA-sequencing expression of MMTV-Neu mouse mammary tumors

Project description:We use RNA-seq to measure gene expression from mammary tumors from untreated MMTV-Neu mice.

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Changes in Gene expression during the development and progression of mammary tumors in MMTV-Wnt-1 and MMTV-Neu TG mice

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Project description:The objective of this study was to determine the effect of Thyroid Hormone Responsive Protein Spot14 (Spot14) overexpression on the gene expression profiles of tumors from MMTV-Neu mice. Hemizygous MMTV-Neu and MMTV-Spot14 mice were bred and 1 cm tumors from Neu control or Neu/Spot14 bitransgenic offspring were profiled using Affymetrix gene arrays. Tumors from Neu/Spot14 mice emerged significantly earlier than controls, but expressed many genes associated with lactogenic differentiation and were not highly metastatic. These results from the mouse model are consistent with observations from primary human breast tumors, which indicate that high Spot14 gene expression was directly correlated with a luminal subtype and a positive ER status. Overexpression of Spot14 in cultured mammary epithelial cells stimulated proliferation but not differentiation. Together, these data suggest that, in vivo, Spot14 is expressed in well-differentiated cells, and promotes the expansion of this population in the context of oncogenic signaling pathway activation. Microarray analysis was performed on 13 mammary tumors from MMTV-Neu mice and 9 tumors from MMTV-Neu/MMTV-Spot14 mice.

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