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

• Published in: Molecular and cellular endocrinology 2015-10, Vol.414, p.91-98
• Main Authors: Malinen, Marjo, Toropainen, Sari, Jääskeläinen, Tiina, Sahu, Biswajyoti, Jänne, Olli A., Palvimo, Jorma J.
• Format: Article
• Language: English
• Subjects: Androgen receptor; Binding Sites; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cell Line, Tumor; Cell Proliferation; Cell Survival; ChIP-seq; Chromatin - metabolism; Chromatin binding; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Humans; Male; Molecular apocrine breast cancer cell; PIAS1; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Protein Inhibitors of Activated STAT - metabolism; Receptors, Androgen - chemistry; Receptors, Androgen - metabolism; Small Ubiquitin-Related Modifier Proteins - metabolism
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.07.024

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. •AR regulates growth-associated genes in molecular apocrine breast cancer cells.•PIAS1 plays a target gene-selective coregulatory role for AR in breast cancer cells.•Breast and prostate cancer cell AR cistromes are similar but considerably distinct.