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Muc1 breast cancer

Michael Chalick, Oded Jacobi, Edward Pichinuk, Christian Garbar, Armand Bensussan, Alan Meeker, Ravit Ziv, Tania Zehavi, Nechama I Smorodinsky, John Hilkens, Franz-Georg Hanisch, Daniel B Rubinstein, Daniel H Wreschner
Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM...
2016: PloS One
Maroof Alam, Audrey Bouillez, Ashujit Tagde, Rehan Ahmad, Hasan Rajabi, Takahiro Maeda, Masayuki Hiraki, Yozo Suzuki, Donald Kufe
: Apical-basal polarity and epithelial integrity are maintained in part by the Crumbs (CRB) complex. The C-terminal subunit of MUC1 (MUC1-C) is a transmembrane protein that is expressed at the apical border of normal epithelial cells and aberrantly at high levels over the entire surface of their transformed counterparts. However, it is not known if MUC1-C contributes to this loss of polarity that is characteristic of carcinoma cells. Here it is demonstrated that MUC1-C downregulates expression of the Crumbs complex CRB3 protein in triple-negative breast cancer (TNBC) cells...
September 22, 2016: Molecular Cancer Research: MCR
Shirin Mahmoodi, Navid Nezafat, Abolfazl Barzegar, Monica Negahdaripour, Ali-Reza Nikanfar, Nosratollah Zarghami, Younes Ghasemi
Breast cancer (BC) remains as one of the important causes of cancer deaths among women globally. Therefore, finding an effective treatment for BC is really needed. Cancer immunotherapy, as an emerging field, has a notable role in BC therapy. Peptide vaccines possess an outstanding role among different strategies in cancer immunotherapy. In vaccine design for cancer, induction of cellular and humoral immune responses should be considered. In the current study, cytolytic T lymphocytes (CTL) epitopes were evoked from human epidermal growth factor receptor (HER2), mucin 1 protein (MUC1), and heparanase antigenic proteins; and helper T lymphocytes (HTL) epitopes were determined from survivin protein by various immunoinformatics servers...
September 14, 2016: Current Pharmaceutical Biotechnology
Philip Hepp, Ulrich Andergassen, Bernadette Jäger, Elisabeth Trapp, Marianna Alunni-Fabbroni, Thomas W P Friedl, Nadeschda Hecker, Ralf Lorenz, Peter Fasching, Andreas Schneeweiss, Tanja Fehm, Wolfgang Janni, Brigitte Rack
BACKGROUND: Evidence for the prognostic value of circulating tumor cells (CTCs) in early-stage breast cancer is swiftly increasing. An alternative approach for identifying patients at risk for recurrence is based on the detection of the mucin-1 (MUC1)-based tumor marker CA27.29. Here we report the association of these two prognostic markers before and immediately after chemotherapy (CHT), as well as after 2 and 5 years of follow-up. PATIENTS AND METHODS: The SUCCESS trial compared fluorouracil, epirubicin and cyclophosphamide followed by docetaxel vs...
September 2016: Anticancer Research
Laura Jeffords Moore, Lopamudra Das Roy, Ru Zhou, Priyanka Grover, Shu-Ta Wu, Jennifer M Curry, Lloye M Dillon, Priya M Puri, Mahboubeh Yazdanifar, Rahul Puri, Pinku Mukherjee, Didier Dréau
BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1). We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice...
August 2016: Translational Oncology
Latha B Pathangey, Vani Lakshminarayanan, Vera J Suman, Barbara A Pockaj, Pinku Mukherjee, Sandra J Gendler
Cancer vaccines have often failed to live up to their promise, although recent results with checkpoint inhibitors are reviving hopes that they will soon fulfill their promise. Although mutation-specific vaccines are under development, there is still high interest in an off-the-shelf vaccine to a ubiquitous antigen, such as MUC1, which is aberrantly expressed on most solid and many hematological tumors, including more than 90% of breast carcinomas. Clinical trials for MUC1 have shown variable success, likely because of immunological tolerance to a self-antigen and to poor immunogenicity of tandem repeat peptides...
2016: Biomolecules
Irmi Wiest, Christoph Alexiou, Klaus Friese, Peter Betz, Jutta Tübel, Steffen Goletz, Darius Dian, Udo Jeschke
BACKGROUND: During neoplasia, glycosylation changes. In this setting, mucins, especially mucin 1 (MUC1), become carriers for oncofetal carbohydrates and relieve invasive growth. The recently described tumor-associated MUC1 epitope TA-MUC1 is primarily restricted to malignancies and is overexpressed in these tissues. The humanized monoclonal antibody PankoMab-GEX specifically recognizes TA-MUC1. MATERIALS AND METHODS: Laryngeal cancer specimens (n=125) and normal tissue of head and neck (n=7) were used in this study...
June 2016: Anticancer Research
Padmamalini Thulasiraman, Andrea Butts Johnson
Understanding the link between chemoresistance and cancer progression may identify future targeted therapy for breast cancer. One of the mechanisms by which chemoresistance is attained in cancer cells is mediated through the expression of multidrug resistance proteins (MRPs). Acquiring drug resistance has been correlated to the emergence of metastasis, accounting for the progression of the disease. One of the diagnostic markers of metastatic progression is the overexpression of a transmembrane protein called Mucin 1 (MUC1) which has been implicated in reduced survival rate...
August 2016: International Journal of Oncology
Masayuki Hiraki, Yozo Suzuki, Maroof Alam, Kunihiko Hinohara, Masanori Hasegawa, Caining Jin, Surender Kharbanda, Donald Kufe
Aberrant expression of myeloid cell leukemia-1 (MCL-1) is a major cause of drug resistance in triple-negative breast cancer (TNBC) cells. Mucin 1 (MUC1) is a heterodimeric oncoprotein that is aberrantly overexpressed in most TNBC. The present studies show that targeting the oncogenic MUC1 C-terminal subunit (MUC1-C) in TNBC cells with silencing or pharmacologic inhibition with GO-203 is associated with downregulation of MCL-1 levels. Targeting MUC1-C suppresses the MEK → ERK and PI3K → AKT pathways, and in turn destabilizes MCL-1...
2016: Scientific Reports
H Rajabi, A Tagde, M Alam, A Bouillez, S Pitroda, Y Suzuki, D Kufe
Aberrant expression of the DNA methyltransferases (DNMTs) and disruption of DNA methylation patterns are associated with carcinogenesis and cancer cell survival. The oncogenic MUC1-C protein is aberrantly overexpressed in diverse carcinomas; however, there is no known link between MUC1-C and DNA methylation. Our results demonstrate that MUC1-C induces the expression of DNMT1 and DNMT3b, but not DNMT3a, in breast and other carcinoma cell types. We show that MUC1-C occupies the DNMT1 and DNMT3b promoters in complexes with NF-κB p65 and drives DNMT1 and DNMT3b transcription...
May 23, 2016: Oncogene
Bindong Dai, Yan Hu, JinHong Duan, Xian-Da Yang
Mucin 1 (MUC1) is an important molecular target for cancer treatment because it is overexpressed in most adenocarcinomas. In this study, a new MUC1-targeted drug delivery system was assembled using an aptamer (Apt) that could recognize MUC1 and a DNA tetrahedron (Td) that could carry doxorubicin (Dox) within its DNA structure. The complex thus formed (Apt-Td) had an average size of 12.38 nm and was negatively charged. Similar to the MUC1 aptamer, the Apt-Td could preferentially bind with MUC1-positive MCF-7 breast cancer cells...
May 18, 2016: Oncotarget
Subhani M Okarvi, Ibrahim Al Jammaz
PURPOSE: The goal of this study was to prepare a synthetic peptide derived from breast tumor associated antigen and to evaluate its potential as a breast cancer imaging agent. METHODS: A mucin 1 derived peptide was synthesized by solid-phase peptide synthesis and examined for its radiochemical and metabolic stability. The tumor cell binding affinity of (99m)Tc-MUC1 peptide was investigated on MUC1-positive T47D and MCF7 breast cancer cell lines. In vivo biodistribution was studied in normal Balb/c mice and in vivo tumor targeting and imaging in MCF7 and T47D tumor-bearing nude mice...
July 2016: Nuclear Medicine and Biology
Neda Mansouri, Abolfazl Movafagh, Shahrzad Soleimani, Mohammad Taheri, Mehrdad Hashemi, Atefeh Heidary Pour, Shohreh Alizadeh Shargh, Alireza Mosavi-Jarahi, Zahra Sasaninejad, Hanieh Zham, Parastoo Hajian, Hossein Allah Moradi, Hamid Reza Mirzaei, Hedieh Fardmanesh, Mina Ohadi
The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Jiajia Yuan, Yanyan Li, Tiantian Tian, Na Li, Yan Zhu, Jianling Zou, Jing Gao, Lin Shen
Recent genomewide studies have identified several germline variations associated with gastric cancer. The aim of the present study was to identify, in a Chinese Han population, the individual and combined effects of those single nucleotide polymorphisms (SNPs) that increase the risk of early-onset gastric cancer. We conducted a case-control study comprising 116 patients with gastric cancer as well as 102 sex- and age-matched controls and confirmed that the SNPs MUC1 (mucin 1) rs9841504 and ZBTB20 (zinc finger and BTB domain containing 20) rs4072037 were associated with an increased gastric cancer risk...
June 7, 2016: Oncotarget
J Xia, J Shi, P Wang, C Song, K Wang, J Zhang, H Ye
Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value...
June 2016: Scandinavian Journal of Immunology
Seyed Mohammad Taghdisi, Noor Mohammad Danesh, Mohammad Ramezani, Parirokh Lavaee, Seyed Hamid Jalalian, Rezvan Yazdian Robati, Khalil Abnous
Clinical use of epirubicin (Epi) in the treatment of cancer has been limited, due to its cardiotoxicity. Targeted delivery of chemotherapeutic agents could increase their efficacy and reduce their off-target effects. High drug loading and excellent stability of DNA dendrimers make these DNA nanostructures unique candidates for biological applications. In this study a modified and promoted dendrimer using three kinds of aptamers (MUC1, AS1411 and ATP aptamers) was designed for targeted delivery of Epi and its efficacy was evaluated in target cells including MCF-7 cells (breast cancer cell) and C26 cells (murine colon carcinoma cell)...
May 2016: European Journal of Pharmaceutics and Biopharmaceutics
Annika Weigand, Anja M Boos, Kereshmeh Tasbihi, Justus P Beier, Paul D Dalton, Michael Schrauder, Raymund E Horch, Matthias W Beckmann, Pamela L Strissel, Reiner Strick
BACKGROUND: There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors...
2016: Breast Cancer Research: BCR
Carlo Fremd, Stefan Stefanovic, Philipp Beckhove, Maria Pritsch, Hendry Lim, Markus Wallwiener, Joerg Heil, Michael Golatta, Joachim Rom, Christof Sohn, Andreas Schneeweiss, Florian Schuetz, Christoph Domschke
Considering the diverse functions of B cells, responses to tumor-associated antigens (TAA) have been thought to be the main source of B cell-mediated antitumor immunity. Polymorphic epithelial mucin (MUC1) is considered one of the most specific TAA in patients with breast cancer. The present study aims to dissect the level and subclasses of naturally occurring anti-MUC1 antibodies in regard to tumor biologic parameters, clinical characteristics and overall survival. In 288 primary, non-metastatic breast cancer patients, pretreatment serum levels of anti-MUC1 immunoglobulin G (IgG) and its subclasses G1-4 as well as immunoglobulin M (IgM) were analyzed via ELISA...
2016: Oncoimmunology
Masanori Hasegawa, Hidekazu Takahashi, Hasan Rajabi, Maroof Alam, Yozo Suzuki, Li Yin, Ashujit Tagde, Takahiro Maeda, Masayuki Hiraki, Vikas P Sukhatme, Donald Kufe
The xCT light chain of the cystine/glutamate transporter (system XC-) is of importance for the survival of triple-negative breast cancer (TNBC) cells. The MUC1-C transmembrane oncoprotein is aberrantly overexpressed in TNBC and, like xCT, has been linked to maintaining glutathione (GSH) levels and redox balance. However, there is no known interaction between MUC1-C and xCT. Here we show that silencing MUC1-C is associated with decreases in xCT expression in TNBC cells. The results demonstrate that MUC1-C forms a complex with xCT and the CD44 variant (CD44v), which interacts with xCT and thereby controls GSH levels...
March 15, 2016: Oncotarget
Morena Antonilli, Hassan Rahimi, Valeria Visconti, Chiara Napoletano, Ilary Ruscito, Ilaria Grazia Zizzari, Salvatore Caponnetto, Giacomo Barchiesi, Roberta Iadarola, Luca Pierelli, Aurelia Rughetti, Filippo Bellati, Pierluigi Benedetti Panici, Marianna Nuti
Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months...
April 2016: International Journal of Oncology
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