title: Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast cancer cells.
abstract: 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 proliferation being among the most enriched functions. Silencing of the coregulator SUMO ligase PIAS1 in MDA-MB453 cells influenced AR function in a target-selective fashion. An anti-apoptotic effect of the silencing suggests involvement of the PIAS1 in the regulation of cell death and survival pathways. In sum, apocrine breast cancer and prostate cancer cells share a core AR cistrome and target gene signature linked to cancer cell growth, and PIAS1 plays a similar coregulatory role for AR in both cancer cell types.
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Malinen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Toropainen
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Jääskeläinen
authors.affiliation: Institute of Biomedicine, Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Biswajyoti
authors.initials: B
authors.lastname: Sahu
authors.affiliation: Institute of Biomedicine, Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
authors.affiliation: Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: jorma.palvimo@uef.fi.
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
mesh_terms: D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism*; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
chemical_list: C410798:AR protein, human; D002843:Chromatin; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011944:Receptors, Androgen; D025841:Small Ubiquitin-Related Modifier Proteins
keywords: Androgen receptor; ChIP-seq; Chromatin binding; Gene expression; Molecular apocrine breast cancer cell; PIAS1