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Kai Li, Yongmin Guo, Xiong Yang, Zhihong Zhang, Changwen Zhang, Yong Xu
The transcription factor E74-like factor 5 (ELF5) is a potent antioncogene that can prevent epithelial-mesenchymal transition (EMT) and metastasis in prostate cancer (PCa). However, little is known how it suppress the tumor growth and if it can interact with androgen receptor (AR). In this study, we find that the ELF5 is frequently expressed in AR activated PCa cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. In addition, the interaction between ELF5 and AR is androgen-dependent...
March 13, 2017: Scientific Reports
Justin Grassmeyer, Malini Mukherjee, Jennifer deRiso, Casey Hettinger, Monica Bailey, Satrajit Sinha, Jane E Visvader, Haotian Zhao, Eric Fogarty, Kameswaran Surendran
The mammalian kidney collecting ducts are critical for water, electrolyte and acid-base homeostasis and develop as a branched network of tubular structures composed of principal cells intermingled with intercalated cells. The intermingled nature of the different collecting duct cell types has made it challenging to identify unique and critical factors that mark and/or regulate the development of the different collecting duct cell lineages. Here we report that the canonical Notch signaling pathway components, RBPJ and Presinilin1 and 2, are involved in patterning the mouse collecting duct cell fates by maintaining a balance between principal cell and intercalated cell fates...
April 1, 2017: Developmental Biology
Hongchao Yan, Linglin Qiu, Xiaolei Xie, He Yang, Yongli Liu, Xiaoman Lin, Hongxiang Huang
The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3...
March 2017: Oncology Reports
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Takamasa Kawaguchi, Dooseon Cho, Masafumi Hayashi, Tomoyuki Tsukiyama, Koji Kimura, Shuichi Matsuyama, Naojiro Minami, Masayasu Yamada, Hiroshi Imai
Trophectoderm lineage specification is one of the earliest differentiation events in mammalian development. The trophoblast lineage, which is derived from the trophectoderm, mediates implantation and placental formation. However, the processes involved in trophoblastic differentiation and placental formation in cattle remain unclear due to interspecies differences when compared with other model systems and the small repertoire of available trophoblast cell lines. Here, we describe the generation of trophoblast cell lines (biTBCs) from bovine amnion-derived cells (bADCs) using an induced pluripotent stem cell technique...
2016: PloS One
Michaela Willi, Kyung Hyun Yoo, Chaochen Wang, Zlatko Trajanoski, Lothar Hennighausen
Cytokines utilize the transcription factor STAT5 to control cell-specific genes at a larger scale than universal genes, with a mechanistic explanation yet to be supplied. Genome-wide studies have identified putative STAT5-based mammary-specific and universal enhancers, an opportunity to investigate mechanisms underlying their differential response to cytokines. We have now interrogated the integrity and function of both categories of regulatory elements using biological and genetic approaches. During lactation, STAT5 occupies mammary-specific and universal cytokine-responsive elements...
December 1, 2016: Nucleic Acids Research
Akifumi Endo, Daisuke Tomizawa, Yuki Aoki, Tomohiro Morio, Shuki Mizutani, Masatoshi Takagi
The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has rarely been reported. We identified a novel EWSR1-associated chimeric fusion gene in a patient with acute myeloid leukemia harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation...
December 2016: Cancer Science
Rie Sano, Tamiko Nakajima, Yoichiro Takahashi, Rieko Kubo, Momoko Kobayashi, Keiko Takahashi, Haruo Takeshita, Kenichi Ogasawara, Yoshihiko Kominato
The human ABO blood group system is of great importance in blood transfusion and organ transplantation. The ABO system is composed of complex carbohydrate structures that are biosynthesized by A- and B-transferases encoded by the ABO gene. However, the mechanisms regulating ABO gene expression in epithelial cells remain obscure. On the basis of DNase I-hypersensitive sites in and around ABO in epithelial cells, we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays and histone modifications indicated a novel positive regulatory element, designated the +22...
October 21, 2016: Journal of Biological Chemistry
Ivana Jurkovic, Iva Gecek, Anita Skrtic, Jasenka Zmijanac Partl, Tamara Nikuseva Martic, Alan Serman, Danica Galesic Ljubanovic, Ljiljana Serman
OBJECTIVE: The purpose of this study was to measure immunohistochemically the expression of ELF5 protein in term human and rat placentas and in human placentas associated with gestational diabetes (GD) and intrauterine growth restriction (IUGR). METHODS: The results were quantitated stereologically using the stereological variable of volume density. A semiquantitative analysis was performed independently by a certified pathologist. RESULTS: Total expression of ELF5 protein was higher in pathological pregnancies than in corresponding control term placentas, with both methods of quantifications showing similar results...
June 2017: Journal of Maternal-fetal & Neonatal Medicine
Ha Youn Shin, Michaela Willi, Kyung Hyun Yoo, Xianke Zeng, Chaochen Wang, Gil Metser, Lothar Hennighausen
Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers...
August 2016: Nature Genetics
Clare A Flannery, Andrew G Fleming, Gina H Choe, Hanyia Naqvi, Margaret Zhang, Anu Sharma, Hugh S Taylor
Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, progestin exposure increases breast cancer risk in postmenopausal women. Alternatives to progestin include bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated...
October 2016: Endocrinology
Jifeng Liu, Xinlong Luo, Yanli Xu, Junjie Gu, Fan Tang, Ying Jin, Hui Li
BACKGROUND: Intrinsic factors and extrinsic signals which control unlimited self-renewal and developmental pluripotency in embryonic stem cells (ESCs) have been extensively investigated. However, a much smaller number of factors involved in extra-embryonic trophoblast differentiation from ESCs have been studied. In this study, we investigated the role of the single-stranded DNA binding protein, Ssbp3, for the induction of trophoblast-like differentiation from mouse ESCs. METHODS: Gain- and loss-of-function experiments were carried out through overexpression or knockdown of Ssbp3 in mouse ESCs under self-renewal culture conditions...
May 28, 2016: Stem Cell Research & Therapy
Sauryang Kim, Jae Woong Yang, Chungho Kim, Moon Gyo Kim
To elucidate the role of a type II transmembrane serine protease, ST14/Prss14, during breast cancer progression, we utilized publically accessible databases including TCGA, GEO, NCI-60, and CCLE. Survival of breast cancer patients with high ST14/Prss14 expression is significantly poor in estrogen receptor (ER) negative populations regardless of the ratios of ST14/Prss14 to its inhibitors, SPINT1 or SPINT2. In a clustering of 1085 selected EMT signature genes, ST14/Prss14 is located in the same cluster with CDH3, and closer to post-EMT markers, CDH2, VIM, and FN1 than to the pre-EMT marker, CDH1...
June 7, 2016: Oncotarget
Kaori Motomura, Mami Oikawa, Michiko Hirose, Arata Honda, Sumie Togayachi, Hiroyuki Miyoshi, Yasuhide Ohinata, Michihiko Sugimoto, Kuniya Abe, Kimiko Inoue, Atsuo Ogura
Mouse trophoblast stem cells (TSCs) proliferate indefinitely in vitro, despite their highly heterogeneous nature. In this study, we sought to characterize TSC colony types by using methods based on cell biology and biochemistry for a better understanding of how TSCs are maintained over multiple passages. Colonies of TSCs could be classified into four major types: type 1 is compact and dome-shaped, type 4 is flattened but with a large multilayered cell cluster, and types 2 and 3 are their intermediates. A time-lapse analysis indicated that type 1 colonies predominantly appeared after passaging, and a single type 1 colony gave rise to all other types...
June 2016: Biology of Reproduction
Alexander Murray, Arnold R Sienerth, Myriam Hemberger
Gene loci that are hypermethylated and repressed in embryonic (ESCs) but hypomethylated and expressed in trophoblast (TSCs) stem cells are very rare and may have particularly important roles in early developmental cell fate decisions, as previously shown for Elf5. Here, we assessed another member of this small group of genes, Placenta Expressed Transcript 1 (Plet1), for its function in establishing trophoblast lineage identity and modulating trophoblast differentiation. We find that Plet1 is tightly repressed by DNA methylation in ESCs but expressed on the cell surface of TSCs and trophoblast giant cells...
April 28, 2016: Scientific Reports
Lily M Fitzgerald, Eva P Browne, Kevin D Christie, Elizabeth C Punska, Leo O Simmons, Kristin E Williams, Brian T Pentecost, Rahul M Jawale, Christopher N Otis, Kathleen F Arcaro
BACKGROUND: Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti-estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of docking protein 7 (DOK7), and E74-like factor 5 (ELF5), in 21 novel tamoxifen-resistant cell lines and extends the findings to primary and recurrent human breast tumors...
2016: Cancer Cell International
Cheryl Q E Lee, Lucy Gardner, Margherita Turco, Nancy Zhao, Matthew J Murray, Nicholas Coleman, Janet Rossant, Myriam Hemberger, Ashley Moffett
Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP)-treated human ESC and 2102Ep, an embryonal carcinoma cell line...
February 9, 2016: Stem Cell Reports
Kaori Motomura, Kimiko Inoue, Atsuo Ogura
Mouse trophoblast stem cells (TSCs) form colonies of different sizes and morphologies, which might reflect their degrees of differentiation. Therefore, each colony type can have a characteristic gene expression profile; however, the expression levels of internal reference genes may also change, causing fluctuations in their estimated gene expression levels. In this study, we validated seven housekeeping genes by using a geometric averaging method and identified Gapdh as the most stable gene across different colony types...
June 17, 2016: Journal of Reproduction and Development
Lucas L Verardo, Fabyano F Silva, Marcos S Lopes, Ole Madsen, John W M Bastiaansen, Egbert F Knol, Mathew Kelly, Luis Varona, Paulo S Lopes, Simone E F Guimarães
BACKGROUND: Reproductive traits such as number of stillborn piglets (SB) and number of teats (NT) have been evaluated in many genome-wide association studies (GWAS). Most of these GWAS were performed under the assumption that these traits were normally distributed. However, both SB and NT are discrete (e.g. count) variables. Therefore, it is necessary to test for better fit of other appropriate statistical models based on discrete distributions. In addition, although many GWAS have been performed, the biological meaning of the identified candidate genes, as well as their functional relationships still need to be better understood...
2016: Genetics, Selection, Evolution: GSE
Catherine L Piggin, Daniel L Roden, David Gallego-Ortega, Heather J Lee, Samantha R Oakes, Christopher J Ormandy
BACKGROUND: E74-like factor 5 (ELF5) is an epithelial-specific member of the E26 transforming sequence (ETS) transcription factor family and a critical regulator of cell fate in the placenta, pulmonary bronchi, and milk-producing alveoli of the mammary gland. ELF5 also plays key roles in malignancy, particularly in basal-like and endocrine-resistant forms of breast cancer. Almost all genes undergo alternative transcription or splicing, which increases the diversity of protein structure and function...
January 7, 2016: Breast Cancer Research: BCR
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