Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide analysis of PIAS1 on AR gene expression in MDA-MB453

ABSTRACT: The majority of breast cancer subtypes express androgen receptor (AR) in addition to estrogen receptor Î± (ERÎ±). Depending on the breast cancer subtype androgen signaling has either stimulatory or inhibitory roles in breast cancer cell growth. We have mapped AR cistrome in ERÎ± negative human molecular apocrine breast cancer MDA-MB453 cells and analyzed it in relation to the androgen-regulated transcriptome in the same cells. We have also examined the effect of silencing of the coregulator SUMO ligase PIAS1 on the androgen-regulated transcriptome and AR cistrome in MDA-MB453 cells. Our results show that the MDA-MB453 cells share with VCaP prostate cancer cells a core AR cistrome and target gene signature linked to cancer cell growth and that PIAS1 acts as an AR target gene-selective coregulator in MDA-MB453 cells. MDA-MB453 cells were transfected with control siRNA (siNON) or PIAS1 siRNA (siPIAS1) for 72 h and treated 16 h with 10 nM R1881 or vehicle (ethanol). Total RNA was isolated and biological triplicate samples were analyzed by microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: Sari Toropainen

PROVIDER: E-GEOD-70162 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells.

Malinen Marjo M Toropainen Sari S Jääskeläinen Tiina T Sahu Biswajyoti B Jänne Olli A OA Palvimo Jorma J JJ

Molecular and cellular endocrinology 20150726

We have analyzed androgen receptor (AR) chromatin binding sites (ARBs) and androgen-regulated transcriptome in estrogen receptor negative molecular apocrine breast cancer cells. These analyses revealed that 42% of ARBs and 39% androgen-regulated transcripts in MDA-MB453 cells have counterparts in VCaP prostate cancer cells. Pathway analyses showed a similar enrichment of molecular and cellular functions among AR targets in both breast and prostate cancer cells, with cellular growth and prolifera ...[more]

PMID: 26219822

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Project description:The role of androgen in breast cancer development is not fully understood although androgen receptors (AR) have been identified in breast cancer clinical samples and cell lines. However the whole spectra of androgen actions cannot be accounted to the classic AR mode of action and the possible existence of a cell surface AR has been suggested. Indeed androgens like all steroids have been reported to trigger membrane initiated signaling activity and exert specific actions. Androgens acting on the membrane can rapidly activate kinase signaling pathways and ultimately could affect gene expression. However, the molecular nature of membrane androgen binding sites represents another major persisting question. In the present study, we investigated early transcriptional effects of testosterone and the impermeable testosterone-BSA conjugate, in two breast cancer cell lines, in an attempt to decipher specific genes modified in each case, providing evidences about specific membrane initiating actions. Our data indicate that the two agents tested affect the expression of several genes. A group of genes were commonly affected while others were uniquely modified by each agent. In MDA-MB-231 cells, that are AR negative, the majority of genes affected by testosterone were also affected by testosterone-BSA indicating a membrane action. Subsequent analysis revealed that the two agents trigger different molecular pathways and cellular/molecular functions, suggestive of a molecular heterogeneity of membrane and intracellular AR. In addition, the phenotypic interactions of membrane-acting androgen with growth factor were verified at the transcriptomic level. Finally an interesting interplay between membrane-acting androgen with inflammation-related molecules, with potential clinical implications was revealed. Experiment Overall Design: Cell lines and culture conditions Experiment Overall Design: The hormone-sensitive breast cancer cell line T47D (expressing ERÎ±, ERÎ² and AR) and the hormone insensitive breast cancer cell line MDA-MB-231 (expressing only ERÎ²) were purchased from the European Collection of Cell Cultures (Salisbury, UK). T47D cells and MDA-MB-231 were cultured in RPMI-1640 medium, supplemented with 10% charcoal treated fetal bovine serum (FBS), in a humidified atmosphere of 5% CO2 in air, at 37Â°C. Culture media and serum were from Gibco BRL (Life Technologies, Paisley, UK). Experiment Overall Design: Treatment- Gene expression assay Experiment Overall Design: Cells were serum starved for 6 hours and then treated with 10-7M Testosterone or charcoal-treated Testosterone-BSA, for 3 hours. Total RNA was isolated using Nucleospin II columns (Macheray-Nagel, DÃ¼ren, Germany), labeled and hybridized according to the Affymetrix protocol (Affymetrix Gene-Chip Expression Analysis Technical Manual), using the HGU133A plus 2 chip, analyzing a total of 54675 transcripts. Signals were detected by an Affymetrix microarray chip reader.

Dataset Information

Genome-wide analysis of PIAS1 on AR gene expression in MDA-MB453

Publications

Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells.

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