Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Transcript and protein profiling identify signaling, growth arrest, apoptosis and NFκB-survival signatures following GnRH receptor activation.


ABSTRACT: Gonadotrophin-releasing hormone (GnRH) significantly inhibits proliferation of a proportion of cancer cell lines by activating GnRH receptor-G protein signaling. Therefore, manipulation of GnRH receptor signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GnRH receptor activation in sensitive cells (HEK293-GnRHR, SCL60) in in vitro and in vivo settings, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic SCL60 response to the GnRH super-agonist Triptorelin. Early and mid-phase changes (0.5-1.0 h) comprised mainly transcription factors. Later changes (8-24 h) included a GnRH target gene, CGA, and up or down-regulation of transcripts encoding signaling and cell division machinery. Pathway analysis exposed identified altered mitogen-activated protein kinase and cell cycle pathways, consistent with occurrence of G2/M arrest and apoptosis. NFκB pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NFκB (p65) occurred in SCL60 in vitro, and p-NFκB and IκBε were higher in treated xenografts than controls after 4 days Triptorelin. NFκB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GnRH receptor signaling, identifies potential anti-proliferative target genes and implicates the NFκB survival pathway as a node for enhancing GnRH agonist-induced anti-proliferation. 55 samples: 35 SCL60 (15 Control, 20 Treated), 20 HEK293 (12 Control, 8 Treated). Samples collected after 0, 0.5, 1, 2, 8 or 24h after treatment with Triptorelin (100nM) or vehicle control (20% Propylene Glycol solution). SCL60 cells are HEK293 cells stably transfected with a high level of functional rat GnRHR.

ORGANISM(S): Homo sapiens

SUBMITTER: Andrew Sims 

PROVIDER: E-GEOD-27467 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Transcript and protein profiling identifies signaling, growth arrest, apoptosis, and NF-κB survival signatures following GNRH receptor activation.

Meyer Colette C   Sims Andrew H AH   Morgan Kevin K   Harrison Beth B   Muir Morwenna M   Bai Jianing J   Faratian Dana D   Millar Robert P RP   Langdon Simon P SP  

Endocrine-related cancer 20130218 1


GNRH significantly inhibits proliferation of a proportion of cancer cell lines by activating GNRH receptor (GNRHR)-G protein signaling. Therefore, manipulation of GNRHR signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GNRHR activation in sensi  ...[more]

Similar Datasets

2012-12-21 | GSE27467 | GEO
2017-06-13 | GSE89463 | GEO
2019-10-16 | GSE133337 | GEO
2013-09-13 | E-GEOD-34230 | biostudies-arrayexpress
| PRJNA138453 | ENA
2018-06-27 | GSE107914 | GEO
2013-10-04 | E-GEOD-42049 | biostudies-arrayexpress
2013-07-30 | E-GEOD-42587 | biostudies-arrayexpress
2021-05-12 | GSE155273 | GEO
2021-05-12 | GSE155272 | GEO