Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profiles regulated by Stat5a/b vs. Stat3 in human prostate cancer cells.

ABSTRACT: Identification of the molecular changes that promote viability and metastatic behaviour of prostate cancer cells is critical for the development of improved therapeutic interventions for prostate cancer. Stat5a/b and Stat3 are both constitutively active in locally-confined and advanced prostate cancer, and both transcription factors have been reported to be critical for the viability and growth of prostate cancer cells. We used microarrays to compare gene expression profiles regulated by Stat5a/b vs. Stat3 in human prostate cancer cells. DU145 and CWR22Rv1 human prostate cancer cells were transfected with Stat3 siRNA, Stat5a/b siRNA or scramble siRNA as control. After 48 h, the cells were harvested and total RNA was prepared for Affymetrix microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Abhijit Dasgupta

PROVIDER: E-GEOD-17482 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth.

Gu Lei L Dagvadorj Ayush A Lutz Jacqueline J Leiby Benjamin B Bonuccelli Gloria G Lisanti Michael P MP Addya Sankar S Fortina Paolo P Dasgupta Abhijit A Hyslop Terry T Bubendorf Lukas L Nevalainen Marja T MT

The American journal of pathology 20100218 4

Identification of the molecular changes that promote viability and metastatic behavior of prostate cancer is critical for the development of improved therapeutic interventions. Stat5a/b and Stat3 are both constitutively active in locally-confined and advanced prostate cancer, and both transcription factors have been reported to be critical for the viability of prostate cancer cells. We recently showed that Stat3 promotes metastatic behavior of human prostate cancer cells not only in vitro but al ...[more]

PMID: 20167868

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Project description:Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC) and BarrettM-bM-^@M-^Ys adenocarcinomas (BAC) revealed similar STAT3 expression in ESCCs and BACs, but preferentially activated P-STAT3 in ESCCs. In vitro, strong STAT3 activation was seen by EGF-stimulation in OE21 (ESCC) cells, whilst OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 and OE33 cells and reduced cell migration in OE33, but not in OE21 cells. Transcriptome analysis identified STAT3-knockdown associated down-regulation of cell cycle processes and the selective down-regulation of cyclins and cyclin dependent kinaes associated genes in both OE21 and OE33 cells. Moreover, the transcriptome response showed changes in cell migration/invasion related genes that correlated with the associated phenotype measurements. This study demonstrates the importance of STAT3 expression and activation in esophageal carcinomas, whereby the extent differs between ESCCs and BACs. STAT3 knockdown significantly reduces cell proliferation in both types of esophageal cancer cells and inhibits migration in BAC cells. Thus, STAT3 may be further exploited as potential novel therapeutic target for esophageal cancers. The effect of STAT3 knock-down in OE33 and OE21 cells was calculated from three biologically independent experiments. 3x10e4 cells were seeded in triplicate in 24 well-plates and were transfected with twice 100nM STAT3 siRNA (pool of 4 STAT3 sequences, siGENOMEM-BM-.SMARTpoolM-BM-., Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) or SilencerM-BM-. negative siRNA control (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) using 1M-BM-5l DharmaFECT (Dharmacon RNAi Technologies, Thermo Fisher Scientific, Lafayette, USA) transfection reagent for OE33 cells or siPORTTM NeoFXTM (Invitrogen/Life Technologies GmbH, Darmstadt, Germany) transfection reagent for OE21 cells. Differential gene regulation was quantified 72 hours after the first transfection by comparing separately for the OE21 and OE33 cells the STAT3 siRNA replicates and the respective cell lines containing the scrambled siRNA vector.

Dataset Information

Gene expression profiles regulated by Stat5a/b vs. Stat3 in human prostate cancer cells.

Publications

Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth.

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