title: Deep sequencing reveals new aspects of progesterone receptor signaling in breast cancer cells.
abstract: Despite the pleiotropic effects of the progesterone receptor in breast cancer, the molecular mechanisms in play remain largely unknown. To gain a global view of the PR-orchestrated networks, we used next-generation sequencing to determine the progestin-regulated transcriptome in T47D breast cancer cells. We identify a large number of PR target genes involved in critical cellular programs, such as regulation of transcription, apoptosis, cell motion and angiogenesis. Integration of the transcriptomic data with the PR-binding profiling of hormonally treated cells identifies numerous components of the small-GTPases signaling pathways as direct PR targets. Progestin-induced deregulation of the small GTPases may contribute to the PR's role in mammary tumorigenesis. Transcript expression analysis reveals significant expression changes of specific transcript variants in response to the extracellular hormonal stimulus. Using the NET1 gene as an example, we show that the PR can dictate alternative promoter usage leading to the upregulation of an isoform that may play a role in metastatic breast cancer. Future studies should aim to characterize these selectively regulated variants and evaluate their clinical utility in prognosis and targeted therapy of hormonally responsive breast tumors.
authors.affiliation: Department of Biological Applications and Technologies, University of Ioannina, Ioannina, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kougioumtzi
authors.affiliation: Department of Computer Science and Engineering, University of Ioannina, Ioannina, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Tsaparas
authors.affiliation: Laboratory of Clinical Chemistry, School of Medicine, University of Ioannina, Ioannina, Greece; Foundation of Research and Technology-Hellas, Institute of Molecular Biology & Biotechnology, Department of Biomedical Research, Ioannina, Greece.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Magklara
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D011397:Promegestone / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011980:Receptors, Progesterone / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D011980:Receptors, Progesterone; D011397:Promegestone