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Stefan Thiem, Moritz F Eissmann, Emma Stuart, Joachim Elzer, Anna Jonas, Michael Buchert, Matthias Ernst
Temporal and spatial regulation of genes mediated by tissue-specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium-specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA)...
October 12, 2016: Genesis: the Journal of Genetics and Development
Sara Kjaer Bastholm, Mie Hesselund Samson, Naja Becher, Lea Kirstine Hansen, Peter Reimer Stubbe, Ioannis S Chronakis, Ebba Nexo, Niels Uldbjerg
INTRODUCTION: The viscoelastic properties of the cervical mucus plug are considered essential for the occlusion of the cervical canal and thereby for protection against ascending infections during pregnancy. Factors controlling this property are virtually unknown. This study explores a possible role of trefoil factor peptides 1, 2 and 3 (TFF1-3); peptides believed to influence mucus viscosity. MATERIALS AND METHODS: The study is based on spontaneously shed cervical mucus plugs from 14 women in active labor...
October 12, 2016: Acta Obstetricia et Gynecologica Scandinavica
Caroline H Diep, Hannah Ahrendt, Carol A Lange
Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines...
October 2016: Steroids
Cheng-Shyong Wu, Kuo-Liang Wei, Jian-Liang Chou, Chung-Kuang Lu, Ching-Chuan Hsieh, Jora M J Lin, Yi-Fang Deng, Wan-Ting Hsu, Hui-Min David Wang, Chung-Hang Leung, Dik-Lung Ma, Chin Li, Michael W Y Chan
Aberrant Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines...
2016: International Journal of Molecular Sciences
A S Hamy, I Bieche, J Lehmann-Che, V Scott, Ph Bertheau, J M Guinebretière, M C Matthieu, B Sigal-Zafrani, O Tembo, M Marty, B Asselain, F Spyratos, P de Cremoux
PURPOSE: Neoadjuvant systemic therapy (NAC) is currently used in the treatment of stage II/III breast cancer. Pathological complete response as a surrogate endpoint for clinical outcomes is not completely validated for all subgroups of breast cancers. Therefore, there is a need for reliable predictive tests of the most effective treatment. METHODS: We used a combination of predictive clinical, pathological, and gene expression-based markers of response to NAC in a prospective phase II multicentre randomized clinical trial in breast cancer patients, with a long follow-up (8 years)...
October 2016: Breast Cancer Research and Treatment
G J Barrera, G Sanchez Tortolero
Trefoil factors are effector molecules in gastrointestinal tract physiology. Each one improves healing of the gastrointestinal tract. Trefoil factors may be grouped into three classes: the gastric peptides (TFF1), spasmolytic peptide (TFF2) and intestinal trefoil factor (TFF3). Significant amounts of TFF3 are present in human breast milk. Previously, we have reported that trefoil factor 3 isolated from human breast milk produces down regulation of cytokines and promotes human beta defensins expression in intestinal epithelial cells...
2016: Bratislavské Lekárske Listy
Chiao-Yun Lin, Angel Chao, Tzu-Hao Wang, Li-Yu Lee, Lan-Yan Yang, Chia-Lung Tsai, Hsin-Shih Wang, Chyong-Huey Lai
Endometrial cancers expressing estrogen and progesterone receptors respond to hormonal therapy. The disappearance of steroid hormone receptor expression is common in patients with recurrent disease, ultimately hampering the clinical utility of hormonal therapy. Here, we demonstrate for the first time that nucleophosmin (NPM1/B23) suppression can restore the expression of estrogen receptor α (ESR1/ERα) in endometrial cancer cells. Mechanistically, B23 and activator protein-2γ (TFAP2C/AP2γ) form a complex that acts as a transcriptional repressor of ERα...
August 4, 2016: Oncotarget
Junpei Yamaguchi, Mari Mino-Kenudson, Andrew S Liss, Sanjib Chowdhury, Timothy C Wang, Carlos Fernández-Del Castillo, Keith D Lillemoe, Andrew L Warshaw, Sarah P Thayer
BACKGROUND & AIMS: Little is known about the origin of pancreatic intraductal papillary mucinous neoplasms (IPMN). Pancreatic duct glands (PDGs) are gland-like outpouches budding off the main pancreatic ducts that function as progenitor niche for the ductal epithelium; they express gastric mucins and have characteristics of side-branch IPMN. We investigated whether PDGs are a precursor compartment for IPMN and the role of trefoil factor family 2 (TFF2)- a protein expressed by PDGs and the gastric mucosa that are involved in epithelial repair and tumor suppression...
August 11, 2016: Gastroenterology
Goncalo Regalo, Susann Förster, Carlos Resende, Bianca Bauer, Barbara Fleige, Wolfgang Kemmner, Peter M Schlag, Thomas F Meyer, José C Machado, Achim Leutz
: Cancer of the stomach is among the leading causes of death from cancer worldwide. The transcription factor C/EBPβ is frequently overexpressed in gastric cancer and associated with the suppression of the differentiation marker TFF1. We show that the murine C/EBPβ knockout stomach displays unbalanced homeostasis and reduced cell proliferation and that tumorigenesis of human gastric cancer xenograft is inhibited by knockdown of C/EBPβ. Cross-species comparison of gene expression profiles between C/EBPβ-deficient murine stomach and human gastric cancer revealed a subset of tumors with a C/EBPβ signature...
August 13, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Wanjun Lin, Jiajun Huang, Xiaolin Liao, Zhongwen Yuan, Senling Feng, Ying Xie, Wenzhe Ma
Breast cancer, the most frequent cancer in women, is the second leading cause of cancer-related death. Estrogens and estrogen receptors are well recognized to play predominant roles in breast cancer development and growth. Neo-tanshinlactone is a natural product isolated from Salvia miltiorrhiza and showed selective growth inhibition of ER+ breast cancer cell lines as demonstrated by cell proliferation assay and colony formation assay. The selective anti-proliferative effect of neo-tanshinlactone was associated with the induction of apoptosis in ER+ breast cancer cells...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
T J Thomas, Thresia Thomas, Shali John, Hui-Chen Hsu, PingAr Yang, Tuomo A Keinänen, Mervi T Hyvönen
Tamoxifen is the most widely used drug to treat women with estrogen receptor α (ERα)-positive breast cancer. Endoxifen is recognized as the active metabolite of tamoxifen in humans. We studied endoxifen effects on ERα-positive MCF-7 breast cancer cells. Estradiol increased the proliferation of MCF-7 cells by two- to threefold and endoxifen suppressed its effects. Endoxifen suppressed c-myc, c-fos and Tff1 oncogene expression, as revealed by RT-PCR. Estradiol increased the activity of ornithine decarboxylase (ODC) and adenosyl methioninedecarboxylase (AdoMetDC), whereas endoxifen suppressed these enzyme activities...
October 2016: Amino Acids
Nikiana Simigdala, Qiong Gao, Sunil Pancholi, Hanne Roberg-Larsen, Marketa Zvelebil, Ricardo Ribas, Elizabeth Folkerd, Andrew Thompson, Amandeep Bhamra, Mitch Dowsett, Lesley-Ann Martin
BACKGROUND: Therapies targeting estrogenic stimulation in estrogen receptor-positive (ER+) breast cancer (BC) reduce mortality, but resistance remains a major clinical problem. Molecular studies have shown few high-frequency mutations to be associated with endocrine resistance. In contrast, expression profiling of primary ER+ BC samples has identified several promising signatures/networks for targeting. METHODS: To identify common adaptive mechanisms associated with resistance to aromatase inhibitors (AIs), we assessed changes in global gene expression during adaptation to long-term estrogen deprivation (LTED) in a panel of ER+ BC cell lines cultured in 2D on plastic (MCF7, T47D, HCC1428, SUM44 and ZR75...
2016: Breast Cancer Research: BCR
Xiang Liu, Hai-Bin Sheng, Rui Ma, Juan-Mei Yang, Wen-Wei Luo, Xiao-Yu Yang, Dong-Dong Ren, Fang-Lu Chi
Mucous cell metaplasia/hyperplasia in the middle ear epithelium is associated with the occurrence of otitis media with effusion during infections. However, the mechanism by which Notch signaling regulates cell fate in the middle ear epithelium is unclear. The aim of the present study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immunofluorescence. Furthermore, the mRNA expression levels of Notch receptors and ligands were evaluated using reverse transcription polymerase chain reaction (PCR)...
May 2016: Experimental and Therapeutic Medicine
Natalija Eigeliene, Lauri Kangas, Christina Hellmer, Tommi Kauko, Risto Erkkola, Pirkko Härkönen
OBJECTIVE: Ospemifene (Osp) is a novel selective estrogen-receptor modulator (SERM) accepted for the treatment of dyspareunia, a symptom of postmenopausal vulvovaginal atrophy. We aimed to analyze the effects of Osp on human breast tissue (HBT), in comparison with the clinically established SERMs raloxifene (Ral) and tamoxifen (Tam), using ex vivo explant cultures. METHODS: HBT samples were obtained from postmenopausal women undergoing mammoplasty and cultured with or without Osp, Ral, Tam, or 17β-estradiol (E2) for 7 and 14 days, and studied for morphology, proliferation, and apoptosis...
July 2016: Menopause: the Journal of the North American Menopause Society
Vienna Ludovini, Fortunato Bianconi, Annamaria Siggillino, Danilo Piobbico, Jacopo Vannucci, Giulio Metro, Rita Chiari, Guido Bellezza, Francesco Puma, Maria Agnese Della Fazia, Giuseppe Servillo, Lucio Crinò
Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR)...
May 24, 2016: Oncotarget
Fitriya N Dewi, Charles E Wood, Cynthia J Willson, Thomas C Register, Cynthia J Lees, Timothy D Howard, Zhiqing Huang, Susan K Murphy, Janet A Tooze, Jeff W Chou, Lance D Miller, J Mark Cline
Endogenous estrogens influence mammary gland development during puberty and breast cancer risk during adulthood. Early-life exposure to dietary or environmental estrogens may alter estrogen-mediated processes. Soy foods contain phytoestrogenic isoflavones (IF), which have mixed estrogen agonist/antagonist properties. Here, we evaluated mammary gland responses over time in pubertal female cynomolgus macaques fed diets containing either casein/lactalbumin (n = 12) or soy protein containing a human-equivalent dose of 120 mg IF/day (n = 17) for approximately 4...
May 2016: Cancer Prevention Research
Denise A Monahan, Jun Wang, Oukseub Lee, Elizabeth Revesz, Nancy Taft, David Ivancic, Nora M Hansen, Kevin P Bethke, C Zalles, Seema A Khan
PURPOSE: The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. METHODS: 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14...
December 30, 2015: Surgical Oncology
Stefan Thiem, Moritz F Eissmann, Joachim Elzer, Anna Jonas, Tracy L Putoczki, Ashleigh Poh, Paul Nguyen, Adele Preaudet, Dustin Flanagan, Elizabeth Vincan, Paul Waring, Michael Buchert, Andrew Jarnicki, Matthias Ernst
About 5% to 10% of human gastric tumors harbor oncogenic mutations in the KRAS pathway, but their presence alone is often insufficient for inducing gastric tumorigenesis, suggesting a requirement for additional mutagenic events or microenvironmental stimuli, including inflammation. Assessing the contribution of such events in preclinical mouse models requires Cre recombinase-mediated conditional gene expression in stem or progenitor cells of normal and transformed gastric epithelium. We therefore constructed a bacterial artificial chromosome containing transgene (Tg), comprising the regulatory elements of the trefoil factor 1 (Tff1) gene and the tamoxifen-inducible Cre recombinase (CreERT2)-coding sequence...
April 15, 2016: Cancer Research
Margaret E Gatti-Mays, David Venzon, Claudia E Galbo, Andrea Singer, James Reynolds, Erini Makariou, Bhaskar Kallakury, Brandy M Heckman-Stoddard, Larissa Korde, Claudine Isaacs, Robert Warren, Ann Gallagher, Jennifer Eng-Wong
This phase II trial evaluated clinical markers of efficacy and safety of exemestane in postmenopausal women at increased risk for breast cancer. Postmenopausal women (n = 42) at risk for invasive breast cancer received 25 mg exemestane daily for 2 years along with calcium and vitamin D. The primary outcome was change in mammographic density (MD) after one year. Secondary outcomes included change in serum steroid hormones as well as change in trefoil protein 1 (TFF1) and proliferating cell nuclear antigen (PCNA) in breast tissue...
March 2016: Cancer Prevention Research
Nicholes R Candelaria, Ryan Weldon, Selvaraj Muthusamy, Trang Nguyen-Vu, Sridevi Addanki, Paule-Helena Yoffou, Husna Karaboga, Alicia M Blessing, Lakshmi Reddy Bollu, Rajesh C Miranda, Chin-Yo Lin
Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells...
2015: PloS One
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