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Retrovirus breast cancer

Gary L Johanning, Gabriel G Malouf, Xiaofeng Zheng, Francisco J Esteva, John N Weinstein, Feng Wang-Johanning, Xiaoping Su
Human endogenous retroviruses (HERVs), which make up approximately 8% of the human genome, are overexpressed in some breast cancer cells and tissues but without regard to cancer subtype. We, therefore, analyzed TCGA RNA-Seq data to evaluate differences in expression of the HERV-K family in breast cancers of the various subtypes. Four HERV-K loci on different chromosomes were analyzed in basal, Her2E, LumA, and LumB breast cancer subtypes of 512 breast cancer patients with invasive ductal carcinoma (IDC). The results for all four loci showed higher HERV-K expression in the basal subtype, suggesting similar mechanisms of regulation regardless of locus...
February 6, 2017: Scientific Reports
María Gonzalez-Cao, Paola Iduma, Niki Karachaliou, Mariacarmela Santarpia, Julià Blanco, Rafael Rosell
Human endogenous retroviruses (HERVs) are retroviruses that infected human genome millions of years ago and have persisted throughout human evolution. About 8% of our genome is composed of HERVs, most of which are nonfunctional because of epigenetic control or deactivating mutations. However, a correlation between HERVs and human cancer has been described and many tumors, such as melanoma, breast cancer, germ cell tumors, renal cancer or ovarian cancer, express HERV proteins, mainly HERV-K (HML6) and HERV-K (HML2)...
December 2016: Cancer Biology & Medicine
Grzegorz Machnik, Łukasz Bułdak, Jarosław Ruczyński, Tomasz Gąsior, Małgorzata Huzarska, Dariusz Belowski, Magdalena Alenowicz, Piotr Mucha, Piotr Rekowski, Bogusław Okopień
The HERV-W family of human endogenous retroviruses represents a group of numerous sequences that show close similarity in genetic composition. It has been documented that some members of HERV-W-derived expression products are supposed to play significant role in humans' pathology, such as multiple sclerosis or schizophrenia. Other members of the family are necessary to orchestrate physiological processes (eg, ERVWE1 coding syncytin-1 that is engaged in syncytiotrophoblast formation). Therefore, an assay that would allow the recognition of particular form of HERV-W members is highly desirable...
December 6, 2016: Journal of Molecular Recognition: JMR
Giuseppe Mastrangelo, Sofia Pavanello, Emanuela Fadda, Alessandra Buja, Ugo Fedeli
Transcripts of human endogenous retrovirus K are expressed in most breast cancers (BCs). Yellow fever vaccine 17D (YFV) expresses a protein with a closely homologous epitope. Cross-reactive immunity could hypothetically inhibit BC growth at least in women aged around 50 years at diagnosis, in whom the prognosis of BC was found to be better than that in women younger or older. A cohort of 12 804 women who received YFV in the Veneto Region, Italy, was divided into two subcohorts according to age at vaccination and followed up through the Veneto Tumor Registry...
November 18, 2016: European Journal of Cancer Prevention
Victor M Bii, Grant D Trobridge
Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations...
October 25, 2016: Cancers
F Cao, M Liu, Q-Z Zhang, R Hao
OBJECTIVE: Phosphatase and actin regulator 4 (PHACTR4) is one member of the largely uncharacterized PHACTR family of protein phosphatase 1 (PP1)-and actin-binding proteins. PHACTR4 is significantly deleted or mutant in many tumor subtypes, such as breast, colorectal, lung, neural, ovarian, and renal cancers. However, the role of PHACTR4 in human hepatocellular carcinoma (HCC) is completely unknown. MATERIALS AND METHODS: Ten paired HCC tissues and adjacent non-cancerous tissues were used to detect the expression PHACTR4...
August 2016: European Review for Medical and Pharmacological Sciences
Fuling Zhou, Ming Li, Yongchang Wei, Kevin Lin, Yue Lu, Jianjun Shen, Gary L Johanning, Feng Wang-Johanning
Human endogenous retrovirus type K (HERV-K) Env protein was previously demonstrated to be overexpressed in human breast cancer (BC) cells and tissues. However, the molecular pathways driving the specific alterations are unknown. We now show that knockdown of its expression with an shRNA (shRNAenv) blocked BC cell proliferation, migration, and invasion. shRNAenv transduction also attenuated the ability of BC cells to form tumors, and notably prevented metastasis. Mechanistically, downregulation of HERV-K blocked expression of tumor-associated genes that included Ras, p-RSK, and p-ERK...
August 20, 2016: Oncotarget
Kimberly S Lucenay, Iman Doostan, Cansu Karakas, Tuyen Bui, Zhiyong Ding, Gordon B Mills, Kelly K Hunt, Khandan Keyomarsi
Cyclin E is altered in nearly a third of invasive breast cancers where it is a powerful independent predictor of survival in women with stage I-III disease. Full-length cyclin E is posttranslationally cleaved into low molecular weight (LMW-E) isoforms, which are tumor-specific and accumulate in the cytoplasm because they lack a nuclear localization sequence. We hypothesized that aberrant localization of cytosolic LMW-E isoforms alters target binding and activation ultimately contributing to LMW-E-induced tumorigenicity...
April 15, 2016: Cancer Research
Hyoung Jin Kim, Byung-In Moon, Jun Woo Lee, Seung Cheol Kim, Hong-Jin Kim
In the present study, the correlation between the antibody response against human endogenous retrovirus K (HERV-K) envelope and human age was investigated. Antibody levels were compared in groups in their 20s (n = 25), 30s (n = 39), 40s (n = 68), 50s (n = 32), and 60s and over (n = 25), which included healthy individuals and breast cancer and/or cervical cancer patients. It appeared that both IgM and IgG responses against the HERV-K envelope fell with increasing age. There were no differences in anti-HERV-K envelope antibody levels between healthy individuals and cancer patients...
April 5, 2016: Oncotarget
Marian P Laderoute
The majority of chronic diseases in the aging adult are thought to relate to immune aging characterized by dominant immunosuppression and paradoxically, concomitant inflammation. This is known collectively as immunosenescence. The main change thought to be controlling immune aging is the age-related decline in dehydroepiandrosterone (DHEA) and corresponding increase in cortisol; the net effect which decreases the DHEA/cortisol ratio. Exactly how this translates to immunosuppression and concomitant inflammation remains unclear...
December 2015: Discovery Medicine
Bodo C Melnik
Single-nucleotide polymorphisms within intron 1 of the FTO (fat mass and obesity-associated) gene are associated with enhanced FTO expression, increased body weight, obesity and type 2 diabetes mellitus (T2DM). The N (6) -methyladenosine (m(6)A) demethylase FTO plays a pivotal regulatory role for postnatal growth and energy expenditure. The purpose of this review is to provide translational evidence that links milk signaling with FTO-activated transcription of the milk recipient. FTO-dependent demethylation of m(6)A regulates mRNA splicing required for adipogenesis, increases the stability of mRNAs, and affects microRNA (miRNA) expression and miRNA biosynthesis...
December 21, 2015: Journal of Translational Medicine
Chris G Twitty, Oscar R Diago, Daniel J Hogan, Cindy Burrascano, Carlos E Ibanez, Douglas J Jolly, Derek Ostertag
Toca 511 is a modified retroviral replicating vector based on Moloney γ-retrovirus with an amphotropic envelope. As an investigational cancer treatment, Toca 511 preferentially infects cancer cells without direct cell lysis and encodes an enhanced yeast cytosine deaminase that converts the antifungal drug 5-fluorocytosine to the anticancer drug, 5-fluorouracil. A panel of established human cancer cell lines, derived from glioblastoma, colon, and breast cancer tissue, was used to evaluate parameters critical for effective anticancer activity...
February 2016: Human Gene Therapy Methods
Fuling Zhou, Janani Krishnamurthy, Yongchang Wei, Ming Li, Kelly Hunt, Gary L Johanning, Laurence Jn Cooper, Feng Wang-Johanning
We have previously reported that human endogenous retrovirus-K (HERV-K) envelope (env) protein is a tumor-associated antigen (TAA) for cancer vaccines, and that its antibodies (mAbs) possess antitumor activity against cancer. In this study, a chimeric antigen receptor (CAR) specific for HERV-K env protein (K-CAR) was generated using anti-HERV-K mAb. K-CAR T cells from peripheral blood mononuclear cells (PBMCs) of 9 breast cancer (BC) patients and 12 normal donors were able to inhibit growth of, and to exhibit significant cytotoxicity toward, BC cells but not MCF-10A normal breast cells...
November 2015: Oncoimmunology
Mi-Hye Hwang, Xiu Juan Li, Jung Eun Kim, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
OBJECTIVE: The aim of this study was to explore the therapeutic effect of natural killer (NK) cells on human doxorubicin-sensitive and resistant breast adenocarcinoma. METHODS: Human doxorubicin-sensitive and resistant breast cancer cell lines (MCF-7 and MCF-7/ADR) were tagged with renilla luciferase (Rluc) (MCF-7/RC and MCF-7/ADR/RC). NK cells were tagged with enhanced firefly luciferase (effluc) using a recombinant retrovirus transfection (NKF). Expression of Rluc, effluc, and NK cell surface markers CD16, CD56 as well as death receptors, DR4 and DR5, were assessed by using flow cytometry...
2015: PloS One
Maricruz Anaya-Ruiz, Martin Perez-Santos
BACKGROUND: To analyze multi-source data including publications and patents, and try to draw the whole landscape of the research and development community in the field of gene therapy for breast cancer. MATERIALS AND METHODS: Publications and patents were collected from the Web of science and databases of the five major patent offices of the world, respectively. Bibliometric methodologies and technology are used to investigate publications/patents, their contents and relationships...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Rafael Contreras-Galindo, Mark H Kaplan, Derek Dube, Marta J Gonzalez-Hernandez, Susana Chan, Fan Meng, Manhong Dai, Gilbert S Omenn, Scott D Gitlin, David M Markovitz
UNLABELLED: Human endogenous retroviruses (HERV) make up 8% of the human genome. While the youngest of these retroviruses, HERV-K(HML-2), termed HK2, is able to code for all viral proteins and produce virus-like particles, it is not known if these virus particles package and transmit HK2-related sequences. Here, we analyzed the capacity of HK2 for packaging and transmitting HK2 sequences. We created an HK2 probe, termed Bogota, which can be packaged into HK2 viruses, and transfected it into cells that make HK2 particles...
July 2015: Journal of Virology
Juliet Rashidian, Erwan Le Scolan, Xiaodan Ji, Qingwei Zhu, Melinda M Mulvihill, Daniel Nomura, Kunxin Luo
Ski, the transforming protein of the avian Sloan-Kettering retrovirus, inhibits transforming growth factor-β (TGF-β)/Smad signaling and displays both pro-oncogenic and anti-oncogenic activities in human cancer. Inhibition of TGF-β signaling is likely responsible for the pro-oncogenic activity of Ski. We investigated the mechanism(s) underlying the tumor suppressor activity of Ski and found that Ski suppressed the activity of the Hippo signaling effectors TAZ and YAP to inhibit breast cancer progression. TAZ and YAP are transcriptional coactivators that can contribute to cancer by promoting proliferation, tumorigenesis, and cancer stem cell expansion...
February 10, 2015: Science Signaling
Kimberly R Holloway, Vidya C Sinha, Michael J Toneff, Wen Bu, Susan G Hilsenbeck, Yi Li
While most breast cancers are thought to arise from the luminal layer of the breast tissue, it remains unclear which specific cells in the luminal layer are the cells of origin of breast cancer. We have previously reported that WAP-positive luminal epithelial cells are at increased susceptibility to tumor initiation by ErbB2 compared to the bulk population, while the mammary cells with canonical Wnt signaling activity fail to evolve into tumors upon ErbB2 activation. Here, we used retrovirus to introduce ErbB2 into the Krt6a-positive mammary progenitor subset of the luminal epithelium and, for comparison, into the mammary luminal epithelium indiscriminately...
2015: PloS One
Melissa N Scheiber, Patricia M Watson, Tihana Rumboldt, Connor Stanley, Robert C Wilson, Victoria J Findlay, Paul E Anderson, Dennis K Watson
ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer...
October 2014: Neoplasia: An International Journal for Oncology Research
Brian Salmons, James S Lawson, Walter H Günzburg
Evidence is accumulating that one or more beta-retrovirus is associated with human breast cancer. Retroviruses can exist as an infectious (exogenous) virus or as a part of the genetic information of cells due to germline integration (endogenous). An exogenous virus with a genome that is highly homologous to mouse mammary tumour virus is gaining acceptance as possibly being associated with human breast cancer, and recently furnished evidence is discussed in this article, as is the evidence for involvement of an endogenous human beta-retrovirus, HERV-K...
December 2014: Journal of General Virology
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