Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses [Expt: PLZF_HEK]

ABSTRACT: Within the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. In this dataset, we include the expression data obtained from stable PLZF overexpression in HEK293T cells. Three intervention samples and three control samples were analyzed. We generated the following pairwise comparisons using Chipinspector (Genomatix Software GmbH) and a FDR of 1%. ChipInspector carries out significance analysis on the single probe level. Normalized probe set level data not provided for individual Sample records. Processed data is available on Series record.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniela Zaade

PROVIDER: E-GEOD-39961 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.

Zaade Daniela D Schmitz Jennifer J Benke Eileen E Klare Sabrina S Seidel Kerstin K Kirsch Sebastian S Goldin-Lang Petra P Zollmann Frank S FS Unger Thomas T Funke-Kaiser Heiko H

PloS one 20130304 3

The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATP ...[more]

PMID: 23469216

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Project description:Endometrial cancer is the most commonly diagnosed gynecologic malignancy in women after breast, lung and colorectal cancer. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer is on the rise. Considerable research effort has therefore been placed on understanding the pathogenesis of this disease to combat this growing issue. There is now emerging evidence to suggest a putative role for dysregulation of the renin angiotensin system (RAS) and in particular the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. Support for this notion arises from previous literature implicating (P)RR in cancer pathophysiology (e.g., breast cancer and pancreatic carcinoma) by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. In view of these data, we aimed to investigate the functional role of (P)RR in human endometrial cancer progression and development. To this end, we employed an siRNA-mediated knock down approach to abrogate (P)RR expression in the immortalized endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1A to explore the role of (P)RR in cellular proliferation and cellular viability. To further extend these analyses we also carried out a sophisticated proteomic screen, that investigated the potential pathways via which (P)RR is acting in endometrial cancer physiology. These data confirmed that (P)RR is critical for endometrial cell cancer development, contributing to both its proliferative capacity and in the maintenance cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets in the treatment of this cancer. Finally we contend that (P)RR, in its soluble form (s(P)RR) in blood, may have substantial potential as a novel biomarker for cancer diagnosis and prognosis prediction going forward.

Dataset Information

Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses [Expt: PLZF_HEK]

Publications

Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.

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