Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression of LNCaP cells grown in 2D cultures and polyethlene glycol-based hydrogels with the presence of synthetic androgen, R1881

ABSTRACT: Analysis of LNCaP cell molecular differences and their response to R1881 in 2D and 3D cultures. Androgen regulated genes were differentially expressed between 2D and 3D cultures. These results provide insights into factors that influence the expression of androgen regulated genes In this study, LNCaP cells cultured in tissue culture plastic (2D) and in the hydrogel (3D) were maintained up to 3 days and 24 days respectively in serum containing media before they were androgen-starved for 48 hours. Cells were either treated with 1nM R1881 or continued to be androgen-deprived (without R1881 with 0.008% ethanol) for another 48 hours prior to cell harvest for gene expression analysis. Biological triplicates were prepared for each condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Colleen Nelson

PROVIDER: E-GEOD-33610 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment.

Sieh Shirly S Taubenberger Anna V AV Rizzi Simone C SC Sadowski Martin M Lehman Melanie L ML Rockstroh Anja A An Jiyuan J Clements Judith A JA Nelson Colleen C CC Hutmacher Dietmar W DW

PloS one 20120905 9

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited ...[more]

PMID: 22957009

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Project description:Androgens drive the onset and progression of prostate cancer (PCa) by modulating androgen receptor (AR) transcriptional activity. Although several microarray-based studies have identified androgen-regulated genes, here we identify in-parallel global androgen-dependent changes in both gene and alternative mRNA isoform expression by exon-level analyses of the LNCaP transcriptome. While genome-wide gene expression changes correlated well with previously-published studies, we additionally uncovered a subset of 226 novel androgen-regulated genes. Gene expression pathway analysis of this subset revealed gene clusters associated with, and including the tyrosine kinase LYN, as well as components of the mTOR (mammalian target of rapamycin) pathway, which is commonly dysregulated in cancer. We also identified 1279 putative androgen-regulated alternative events, of which 325 (~25%) mapped to known alternative splicing events or alternative first/last exons. We selected 30 androgen-dependent alternative events for RT-PCR validation, including mRNAs derived from genes encoding tumour suppressors and cell cycle regulators. Of seven positively-validating events (~23%), five events involved transcripts derived from known AR gene targets. In particular, we found a novel androgen-dependent mRNA isoform derived from an alternative internal promoter within the TSC2 tumour suppressor gene, which is predicted to encode a protein lacking an interaction domain required for mTOR inhibition. We confirmed that expression of the alternative TSC2 mRNA isoform was directly regulated by androgens. Furthermore, by chromatin immunoprecipitation, we observed recruitment of AR to the alternative promoter region at early timepoints following androgen stimulation, which correlated with expression of alternative transcripts. Together, our data suggest that alternative mRNA isoform expression might mediate the cellular response to androgens, and may have roles in clinical PCa. Total 8 samples were analysed. 4 control (LNCaP cells grown in RPMI-1640 media with charcoal-stripped 10% FBS devoid of steroids) and 4 treatment (LNCaP cells grown in media devoid of steroid, and subsequently treated with 10nM R1881 synthetic androgen analogue for 24 hours).

Dataset Information

Gene expression of LNCaP cells grown in 2D cultures and polyethlene glycol-based hydrogels with the presence of synthetic androgen, R1881

Publications

Phenotypic characterization of prostate cancer LNCaP cells cultured within a bioengineered microenvironment.

Similar Datasets

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