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

Marjo Malinen; Sari Toropainen; Tiina Jääskeläinen; Biswajyoti Sahu; Olli A Jänne; Jorma J Palvimo

doi:10.1016/j.mce.2015.07.024

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

Mol Cell Endocrinol. 2015 Oct 15:414:91-8. doi: 10.1016/j.mce.2015.07.024. Epub 2015 Jul 26.

Authors

Marjo Malinen¹, Sari Toropainen¹, Tiina Jääskeläinen², Biswajyoti Sahu³, Olli A Jänne⁴, Jorma J Palvimo⁵

Affiliations

¹ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
² Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.
³ Institute of Biomedicine, Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
⁴ Institute of Biomedicine, Physiology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
⁵ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: [email protected].

PMID: 26219822
DOI: 10.1016/j.mce.2015.07.024

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.

Keywords: Androgen receptor; ChIP-seq; Chromatin binding; Gene expression; Molecular apocrine breast cancer cell; PIAS1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Cell Line, Tumor
Cell Proliferation
Cell Survival
Chromatin / metabolism*
Female
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic
Humans
Male
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
Protein Inhibitors of Activated STAT / metabolism*
Receptors, Androgen / chemistry
Receptors, Androgen / metabolism*
Small Ubiquitin-Related Modifier Proteins / metabolism*

Substances

AR protein, human
Chromatin
PIAS1 protein, human
Protein Inhibitors of Activated STAT
Receptors, Androgen
Small Ubiquitin-Related Modifier Proteins