NR2F2 Orphan Nuclear Receptor is Involved in Estrogen Receptor Alpha-Mediated Transcriptional Regulation in Luminal A Breast Cancer Cells
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Erdos, Edina; Balint, Balint Laszlo
Abstract
Nuclear Receptor Subfamily 2 Group F Member 2 (NR2F2) is a member of the steroid/thyroid hormone receptor superfamily with a crucial role in organogenesis, angiogenesis, cardiovascular development and tumorigenesis. However, there is limited knowledge about the cistrome and transcriptome of NR2F2 in breast cancer. In this study, we mapped the regulatory mechanism by NR2F2 using functional genomic methods. To investigate the clinical significance of NR2F2 in breast cancer, The Cancer Genome Atlas (TCGA) data were used. These results show that a high NR2F2 is associated with better survival of a specific subset of patients, namely those with luminal A breast cancer. Therefore, genome-wide NR2F2 and estrogen receptor alpha (ER alpha) binding sites were mapped in luminal A breast cancer cells using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq), revealing that most NR2F2 overlap with ER alpha that are co-occupied by forkhead box A1 (FOXA1) and GATA binding protein 3 (GATA3) in active enhancer regions. NR2F2 overlaps with highly frequent ER alpha chromatin interactions, which are essential for the formation of ER alpha-bound super-enhancers. In the process of the transcriptome profiling of NR2F2-depleted breast cancer cells such differentially expressed genes have been identified that are involved in endocrine therapy resistance and are also ER alpha target genes. Overall, these findings demonstrate that the NR2F2 nuclear receptor has a key role in ER alpha-mediated transcription and it can offer a potential therapeutic target in patients with luminal A breast cancer.
Secretory Carcinoma of the Skin Report of 6 Cases, Including a Case With a Novel NFIX-PKN1 Translocation
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Authors: Kastnerova, Liubov; Luzar, Bostjan; Goto, Keisuke; Grishakov, Viktor; Gatalica, Zoran; Kamarachev, Jivko; Martinek, Petr; Hajkova, Veronika; Grossmann, Petr; Imai, Hiroshi; Fukui, Hideaki; Michal, Michal; Kazakov, Dmitry, V
Abstract
Secretory carcinoma of the skin is a rare adnexal carcinoma, which is morphologically and immunohistochemically identical to secretory carcinoma of the breast and is associated with the presence of t (12;15) translocation, resulting in the ETV6-NTRK3 gene fusion. Nineteen cases of primary cutaneous secretory carcinoma have been previously published in the literature. In this study, we describe 6 new cases of secretory carcinoma of the skin. The study group consisted of 5 female patients and 1 male patient, ranging in age from 57 to 98 years (mean: 74.2, median: 74). Locations included the axilla (2), neck, eyelid, thigh, and nipple base, each one. Microscopically, all but 1 tumor were well circumscribed and nonencapsulated and exhibited characteristic abundant secretions within the microcystic and tubular spaces comprised by bland oval, round to cuboidal neoplastic cells. In addition, solid areas and focal pseudopapillae were seen, and, in 1 case, a focal mucinous component with small lakes of mucin containing small tumor nests or tubules of the neoplastic cells was present. The remaining neoplasm was mostly solid and papillary, with only few characteristic lumina containing secretions. Immunohistochemically, all cases expressed S-100 protein, mammaglobin, STAT5, GATA3, and NTRK. ETV6-NTRK3 gene fusion was detected in 5 cases, whereas, in the remaining tumor, a novel NFIX-PKN1 gene fusion was found.