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ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer [NCI-H510A]

ABSTRACT: ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer [NCI-H510A]

PROVIDER: PRJNA1177392 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31103377_1.fastq.gz	Fastqsanger.gz
	SRR31103377_2.fastq.gz	Fastqsanger.gz
	SRR31103378_1.fastq.gz	Fastqsanger.gz
	SRR31103378_2.fastq.gz	Fastqsanger.gz
	SRR31103379_1.fastq.gz	Fastqsanger.gz

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Project description:The management of neuroendocrine tumors (NETs) is very variable, depending on many specific aspects, such as the type of tumor, spread and patient general health. Several advances have been made with the newly developed somatostatin analogues to cure this type of malignancies. Somatostain analogues such as octreotide have been used in clinic to treat patients with neuroendocrine tumors (NETs). However, the molecular mechanism leading either to successful therapy or acquired resistance to the analogues is still to large extent unclear. Patients develop drugs resistance during a long term treatment. Therefore, to identify the pivotal regulatory genes involved in the development of drug resistance is an actual challenge. We studied five human neuroendocrine tumor cell lines, CNDT2.5, KRJ1, QGP-1, NCI H720 and NCI H727. We also investigated a long-term treated CNDT2.5 by using octreotide. We performed gene expression profiling in all the human neuroendocrine cell lines. Keywords: Gene Expression profiling, treatment comparison We investigated 5 human neuroendocrine cell lines, CNDT2.5 and KRJ1, established from ileum NETs, QGP1 by a pancreatic NET, NCI H720 and NCI H727 from bronchopulmonary NETs. CNDT2.5 cell were constantly treated with 1M-BM-5M octreotide for 10 and 16 months. We isolated total RNA (Ambion, PARISM-bM-^DM-" Kit) from 5 WT cell lines and CNDT2.5 treated with octreotide (Santostatin, Novartis). Total RNA was hybridized onto the Affymetrix Human Gene 1.0 ST Array by Affymetrix Uppsala Platform, UU. SE (Uppsala, Sweden). We first wanted to verify whether the different cell lines may become reliable models to study neuroendocrine signaling pathways. The main objective of this project aimed at understanding the mechanisms by which octrotide (Sandostatin, Novartis) alter cellular growth and differentiation of CNDT2.5 cells. We therefore focused on intermediate (10 months) and long stimulation (16 months) events triggered by sandostatin, which lead variation of CNDT.2.5 cells gene expression to identify potential pivotal genes involved in the development of drug resistance in neuroendocrine cells.

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ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer [NCI-H510A]

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