Dataset Information

NCOA6 is a potent prostate cancer suppressor essential for NFY-mediated restriction of EGFR overexpression

ABSTRACT: NCOA6 is a potent prostate cancer suppressor essential for NFY-mediated restriction of EGFR overexpression

PROVIDER: PRJNA655484 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR12395817_1.fastq.gz	Fastqsanger.gz
	SRR12395817_2.fastq.gz	Fastqsanger.gz
	SRR12395818_1.fastq.gz	Fastqsanger.gz
	SRR12395818_2.fastq.gz	Fastqsanger.gz
	SRR12395819_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 51

Similar Datasets

Project description:Basal-like and triple negative breast cancer (TNBC) share common molecular features, poor prognosis and a propensity for metastasis to the brain. Amplification of EGFR occurs in ~50% of basal-like breast cancer and mutations in the epidermal growth factor receptor (EGFR) have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung cancer several different mutations in the EGFR tyrosine kinase domain confer sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic potential of EGFR mutations in breast cells and their potential for targeted therapy is unknown. Constructs containing wild type, G719S or E746-A750 deletion mutant forms of EGFR were transfected into the ‘near normal’ MCF10A breast cells and their tumorigenic derivative, MCF10CA1a. These transfected lines were used to investigate the effects of EGFR over-expression and mutation on proliferation, migration, invasion, response to gefitinib, and tumour formation in vivo. We also carried out copy number analysis and whole exome sequencing of the MCF10A and MCF10CA1a cell lines. Both activating mutations of EGFR increased the proliferative ability of MCF10A and MCF10CA1a cell lines, and increased the anchorage-independent growth and sensitivity to gefitinib in MCF10A cells. In addition, the EGFR-E746-A750 deletion increased the migratory and invasive abilities of the MCF10CA1a cell line in vitro, and greatly increased the formation and growth of MCF10CA1a tumours in vivo. Compared to MCF10A cells, MCF10CA1a cells had large regions of gain on chromosome 9 and the long arm of chromosome 3, deletion in the short arm of chromosome 7, and mutations in many genes implicated in cancer. The EGFR E746-A750 deletion mutation, and to a lesser extent G719S, greatly enhance the oncogenic properties of MCF10A cell line, and increase sensitivity to gefitinib. Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more tumourigenic in vivo it is not accompanied by increased sensitivity to gefitinib, perhaps because of additional mutations, including the PIK3CA H1047R mutation, that the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for EGFR mutations may prove useful for directing therapy but, as in non-small cell lung cancer cancer, accompanying mutations in PIK3CA may confer gefitinib resistance.

Dataset Information

NCOA6 is a potent prostate cancer suppressor essential for NFY-mediated restriction of EGFR overexpression

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets