Genes and Cancer最新文献

{"title":"Genomic alterations of Tenascin C in highly aggressive prostate cancer: a meta-analysis.","authors":"Prachi Mishra, Michael A Kiebish, Jennifer Cullen, Alagarsamy Srinivasan, Aliyah Patterson, Rangaprasad Sarangarajan, Niven R Narain, Albert Dobi","doi":"10.18632/genesandcancer.196","DOIUrl":"10.18632/genesandcancer.196","url":null,"abstract":"<p><p>Tenascin C (TNC), an extra-cellular matrix (ECM) family gene, is expressed in several cancer tissues of breast, lung, colon, and gastrointestinal tract leading to proliferation, migration, invasion, angiogenesis and metastasis, but its role in tumorigenesis of prostate cancer is poorly understood. We took a meta-analysis approach to characterize the alterations of TNC gene in prostate cancer using publicly available databases (cBioportal Version 2.2.0, http://www.cBioportal.org/index.do). The analysis identified TNC alterations (gene amplification) significantly in the neuroendocrine prostate cancer dataset (Trento/Broad/Cornell, <i>N</i> = 114), which was further validated in other prostate cancer datasets, including The Cancer Genome Atlas (TCGA) prostate cancer (2015). In the TCGA prostate cancer dataset (<i>N</i> = 498), high TNC (alteration frequency, 36%) revealed a strong association with high diagnostic Gleason score. Genomic alterations of TNC was also significantly associated (<i>P</i> < 0.05) with expression level of genes from NOTCH, SOX and WNT family, implicating a link between TNC and poorly differentiated aggressive phenotype in NEPC. TCGA prostate adenocarcinoma cases with TNC alteration also demonstrated prominent decrease in disease-free survival (<i>P</i> = 0.0637). These findings indicate a possible association of TNC to the aggressive subtype of prostate cancer and warrant further functional studies to evident the involvement of TNC in prostate cancer progression.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"10 1","pages":"150-159"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67543923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How a disruption of the competition between HIF-1 and p53 for limiting p300/CBP by latent viruses can cause disease.","authors":"Hanan Polansky,&nbsp;Hava Schwab","doi":"10.18632/genesandcancer.178","DOIUrl":"https://doi.org/10.18632/genesandcancer.178","url":null,"abstract":"CBP and p300 are considered the most heavily connected coactivators in the mammalian protein-protein interaction network [1] with at least 315 different cellular and viral interacting partners [2]. CBP and p300 are histone acetyltransferases that control the transcription of numerous genes in humans, viruses, and other species. CBP/p300 is a 300 kDa protein that has a CH2 domain, which contains its acetyltransferase activity, and five binding domains [3]. Although two separate genes encode CBP and p300, they share a 61% sequence identity, and are often mentioned together as CBP/p300 [3]. Many studies showed that competition for the limiting CBP/p300 is an important mechanism used by the cell to regulate transcription and cellular behavior. This commentary discusses two of these studies [4] [5] and connects the observations reported in these studies to the Microcompetition Model. HIF-1α, a subunit of the hypoxia-inducible factor-1 (HIF-1) transcription factor, is regulated in an oxygendependent manner. Under normal oxygen conditions it is inactive and made at low levels. Under hypoxic conditions, it is stabilized and activated. The tumor suppressor p53 is another protein that is active under hypoxic conditions. Using differential equations and a dimensionless state variable, Zhou et al. [4] determined the effect of p300 on the steady-state concentrations of proteins. They discovered that under hypoxic conditions HIF-1α and tumor suppressor p53 compete for binding to the coactivator p300. They showed that the co-activator p300 is required for full transcriptional activity of both p53 and HIF-1. According to Zhou et al., this competition indicates that p300 is limiting. To investigate the cross-talk between HIF-1α and p53, Ruas et al. [5] performed ChIP analyses to examine the recruitment of CBP to HIF-1α and p53 target gene promoters under hypoxic conditions. The results of the ChIP analyses showed that under this condition the levels of CBP on target gene promoters are reduced compared to the maximum binding levels. Based on these results, Ruas et al. concluded that CBP/p300 is limiting, and that HIF-1α and p53 compete for recruitment of the limiting amounts of CBP/p300 to their target gene promoters, and that this competition affects the transcription of these genes. These studies showed that competition between the cellular transcription factors HIF-1α and p53 for binding the limiting p300 is an important regulator of transcription. According to the Microcompetition Model, a disruption of this regulation can cause many diseases. The Microcompetition Model was first described in the book ‘Microcompetition with Foreign DNA and the Origin of Chronic Disease.’ [6][7] The model centers on one type of disruption of this regulation caused by viruses that include the strong cis-regulatory element found their promoters/enhancers called the N-box. This element binds the cellular p300•GABP transcription complex during the latent phase. Some common viruses ","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"153-154"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36819068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor metabolism regulating chemosensitivity in ovarian cancer.","authors":"Chae Young Han, David A Patten, Richard B Richardson, Mary-Ellen Harper, Benjamin K Tsang","doi":"10.18632/genesandcancer.176","DOIUrl":"10.18632/genesandcancer.176","url":null,"abstract":"<p><p>Elevated metabolism is a key hallmark of multiple cancers, serving to fulfill high anabolic demands. Ovarian cancer (OVCA) is the fifth leading cause of cancer deaths in women with a high mortality rate (45%). Chemoresistance is a major hurdle for OVCA treatment. Although substantial evidence suggests that metabolic reprogramming contributes to anti-apoptosis and the metastasis of multiple cancers, the link between tumor metabolism and chemoresistance in OVCA remains unknown. While clinical trials targeting metabolic reprogramming alone have been met with limited success, the synergistic effect of inhibiting tumor-specific metabolism with traditional chemotherapy warrants further examination, particularly in OVCA. This review summarizes the role of key glycolytic enzymes and other metabolic synthesis pathways in the progression of cancer and chemoresistance in OVCA. Within this context, mitochondrial dynamics (fission, fusion and cristae structure) are addressed regarding their roles in controlling metabolism and apoptosis, closely associated with chemosensitivity. The roles of multiple key oncogenes (Akt, HIF-1α) and tumor suppressors (p53, PTEN) in metabolic regulation are also described. Next, this review summarizes recent research of metabolism and future direction. Finally, we examine clinical drugs and inhibitors to target glycolytic metabolism, as well as the rationale for such strategies as potential therapeutics to overcome chemoresistant OVCA.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"155-175"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36818444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma Par-4 levels and apoptosis in diverse tumors.","authors":"Peng Wang, Ravshan Burikhanov, Rani Jayswal, Heidi L Weiss, Susanne M Arnold, John L Villano, Vivek M Rangnekar","doi":"10.18632/genesandcancer.181","DOIUrl":"10.18632/genesandcancer.181","url":null,"abstract":"<p><p>Chloroquine and hydroxychloroquine (HCQ) are robust inducers of the tumor suppressor Par-4 secretion from normal cells. Secreted Par-4 causes paracrine apoptosis of tumor cells and inhibits metastasis in mice. We report the clinical results with pharmacodynamic analyses of our Phase I trial using neoadjuvant administration of HCQ in patients with surgically removable early stage solid tumors. This was a single-institution trial of oral HCQ (200 or 400 mg twice daily) given for 14 days prior to planned surgery. Dose escalation was based on isotonic regression to model safety and biological effect based on plasma Par-4 analysis. Eight of the nine patients treated with HCQ showed elevation in plasma Par-4 levels over basal levels. No toxicities were observed with these dose regimens. The resected tumors from the eight HCQ-treated patients with elevated plasma Par-4 levels, but not the resected tumor from the patient who failed to induce plasma Par-4 levels, exhibited TUNEL-positivity indicative of apoptosis. Resected tumors from all nine HCQ-treated patients showed p62/sequestosome-1 induction indicative of autophagy-inhibition by HCQ. Our findings indicate that both dose levels of HCQ were well-tolerated and that Par-4 secretion but not induction of the autophagy-inhibition marker p62 correlated with apoptosis induction in patients' tumors.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"190-197"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36819070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic carcinoma cells colonizing the liver modulate the expression of their extracellular matrix genes.","authors":"Khamael M K Al-Taee,&nbsp;Michael Zepp,&nbsp;Irina Berger,&nbsp;Martin R Berger,&nbsp;Hassan Adwan","doi":"10.18632/genesandcancer.179","DOIUrl":"https://doi.org/10.18632/genesandcancer.179","url":null,"abstract":"<p><p>Liver is the main target of pancreatic ductal adenocarcinoma (PDAC) metastasis. Here, a rat model was used for analysing gene expression modulations during liver colonization. ASML PDAC cells were injected to isogenic rats and re-isolated at various stages of liver colonization for RNA isolation or re-cultivation. Microarrays were used for analysing mRNA and miRNA profiles of expres-sion. The results were partially confirmed by (q) RT-PCR and western blot. Selected genes were knocked down by siRNA transfection and the resulting cell behaviour was analysed. The ratio of up- and down regulated genes decreased from 20:1 (early stage) to 1.2:1 (terminal stage). Activation of cancer relevant gene categories varied between stages of liver colonization, with a nadir in the intermediate stage. The cells' environment triggered up to hundredfold changed expression for collagens, matrix metalloproteinases and chemokines. These modulations in mRNA expression were related to respective changes at miRNA levels. Gene expression knockdown of Mmp2 and Ccl20, which were highly modulated in vivo, was correlated with reduced prolif-eration and migration in vitro. Thus, target genes and temporal alterations in expression were identified, which can serve as basis for future therapeutic or diagnostic purposes.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"215-231"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36818446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy.","authors":"Long Long,&nbsp;Xue Zhang,&nbsp;Fuchun Chen,&nbsp;Qi Pan,&nbsp;Pronnaphat Phiphatwatchara,&nbsp;Yuyang Zeng,&nbsp;Honglei Chen","doi":"10.18632/genesandcancer.180","DOIUrl":"https://doi.org/10.18632/genesandcancer.180","url":null,"abstract":"<p><p>Cancer immunotherapy and tumor microenvironment have been at the forefront of research over the past decades. Targeting immune checkpoints especially programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) has made a breakthrough in treating advanced malignancies. However, the low response rate brings a daunting challenge, changing the focus to dig deeply into the tumor microenvironment for alternative therapeutic targets. Strikingly, the inhibitory immune checkpoint lymphocyte activation gene-3 (LAG-3) holds considerable potential. LAG-3 suppresses T cells activation and cytokines secretion, thereby ensuring immune homeostasis. It exerts differential inhibitory impacts on various types of lymphocytes and shows a remarkable synergy with PD-1 to inhibit immune responses. Targeting LAG-3 immunotherapy is moving forward in active clinical trials, and combination immunotherapy of anti-LAG-3 and anti-PD-1 has shown exciting efficacy in fighting PD-1 resistance. Herein, we shed light on the significance of LAG-3 in the tumor microenvironment, highlight its role to regulate different lymphocytes, interplay with other immune checkpoints especially PD-1, and emphasize new advances in LAG-3-targeted immunotherapy.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"176-189"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36819069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole-transcriptome sequencing identified gene expression signatures associated with aggressive clear cell renal cell carcinoma.","authors":"Ken Batai,&nbsp;Elliot Imler,&nbsp;Jayce Pangilinan,&nbsp;Robert Bell,&nbsp;Aye Lwin,&nbsp;Elinora Price,&nbsp;Tijana Milinic,&nbsp;Amit Arora,&nbsp;Nathan A Ellis,&nbsp;Erika Bracamonte,&nbsp;Bruce Seligmann,&nbsp;Benjamin R Lee","doi":"10.18632/genesandcancer.183","DOIUrl":"https://doi.org/10.18632/genesandcancer.183","url":null,"abstract":"<p><p>Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer, yet molecular biomarkers have not been used for the prognosis of ccRCC to aide clinical decision making. This study aimed to identify genes associated with ccRCC aggressiveness and overall survival (OS). Samples of ccRCC tumor tissue were obtained from 33 patients who underwent nephrectomy. Gene expression was determined using whole-transcriptome sequencing. The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) RNA-seq data was used to test association with OS. 290 genes were differentially expressed between tumors with high and low stage, size, grade, and necrosis (SSIGN) score (≥7 <i>vs</i>. ≤3) with <i>P</i> _ADJ<0.05. Four genes, <i>G6PD</i>, <i>APLP1</i>, <i>GCNT3</i>, and <i>PLPP2</i>, were also over-expressed in advanced stage (III and IV) and high grade (3 and 4) ccRCC and tumor with necrosis (<i>P</i> _ADJ<0.05). Investigation stratifying by stage found that <i>APLP1</i> and <i>PLPP2</i> overexpression were significantly associated with poorer OS in the early stage (Quartile 1 vs. Quartile 4, HR = 3.87, 95% CI:1.25-11.97, <i>P</i> = 0.02 and HR = 4.77, 95% CI:1.37-16.57, <i>P</i> = 0.04 respectively). These genes are potential biomarkers of ccRCC aggressiveness and prognosis that direct clinical and surgical management.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"247-256"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/genesandcancer.183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36818448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common ELF1 deletion in prostate cancer bolsters oncogenic ETS function, inhibits senescence and promotes docetaxel resistance.","authors":"Justin A Budka,&nbsp;Mary W Ferris,&nbsp;Matthew J Capone,&nbsp;Peter C Hollenhorst","doi":"10.18632/genesandcancer.182","DOIUrl":"https://doi.org/10.18632/genesandcancer.182","url":null,"abstract":"<p><p>ETS family transcription factors play major roles in prostate tumorigenesis with some acting as oncogenes and others as tumor suppressors. ETS factors can compete for binding at some cis-regulatory sequences, but display specific binding at others. Therefore, changes in expression of ETS family members during tumorigenesis can have complex, multimodal effects. Here we show that ELF1 was the most commonly down-regulated ETS factor in primary prostate tumors, and expression decreased further in metastatic disease. Genome-wide mapping in cell lines indicated that ELF1 has two distinct tumor suppressive roles mediated by distinct cis-regulatory sequences. First, ELF1 inhibited cell migration and epithelial-mesenchymal transition by interfering with oncogenic ETS functions at ETS/AP-1 cis-regulatory motifs. Second, ELF1 uniquely targeted and activated genes that promote senescence. Furthermore, knockdown of ELF1 increased docetaxel resistance, indicating that the genomic deletions found in metastatic prostate tumors may promote therapeutic resistance through loss of both RB1 and ELF1.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"198-214"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36818445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-messenger RNA interactions involving JAK-STAT signaling genes in colorectal cancer.","authors":"Lila E Mullany,&nbsp;Jennifer S Herrick,&nbsp;Lori C Sakoda,&nbsp;Wade Samowitz,&nbsp;John R Stevens,&nbsp;Roger K Wolff,&nbsp;Martha L Slattery","doi":"10.18632/genesandcancer.177","DOIUrl":"https://doi.org/10.18632/genesandcancer.177","url":null,"abstract":"<p><p>JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of messenger RNAs (mRNAs) and miRNAs using RNA-Seq and Agilent Human miRNA Microarray V19.0 data, respectively, using a negative binomial mixed effects model to test 122 JAK-STAT-signaling genes in 217 colorectal cancer (CRC) cases. Overall, 42 mRNAs were differentially expressed with a fold change of >1.50 or <0.67, remaining significant with a false discovery rate of < 0.05; four were dysregulated in microsatellite stable (MSS) tumors, eight were for microsatellite unstable (MSI)-specific tumors. Of these 54 mRNAs, 17 were associated with differential expression of 46 miRNAs, comprising 116 interactions: 16 were significant overall, one for MSS tumors only. Twenty of the 29 interactions with negative beta coefficients involved miRNA seed sequence matches with mRNAs, supporting miRNA-mediated mRNA repression; 17 of these mRNAs encode for receptor molecules. Receptor molecule degradation is an established JAK-STAT signaling control mechanism; our results suggest that miRNAs facilitate this process. Interactions involving positive beta coefficients may illustrate downstream effects of disrupted STAT activity, and subsequent miRNA upregulation.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 5-6","pages":"232-246"},"PeriodicalIF":0.0,"publicationDate":"2018-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36818447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral tumor antigen expression is no longer required in radiation-resistant subpopulation of JCV induced mouse medulloblastoma cells.","authors":"Martina Donadoni,&nbsp;Rahsan Sariyer,&nbsp;Hassen Wollebo,&nbsp;Anna Bellizzi,&nbsp;Ilker Kudret Sariyer","doi":"10.18632/genesandcancer.174","DOIUrl":"https://doi.org/10.18632/genesandcancer.174","url":null,"abstract":"<p><p>The human neurotropic polyomavirus JC, JC virus (JCV), infects the majority of human population during early childhood and establishes a latent/persistent infection for the rest of the life. JCV is the etiologic agent of the fatal demyelinating disease of the central nervous system, progressive multifocal leukoencephalopathy (PML) that is seen primarily in immunocompromised individuals. In addition to the PML, JCV has also been shown to transform cells in culture systems and cause a variety of tumors in experimental animals. Moreover, JCV genomic DNA and tumor antigen expression have been shown in a variety of human tumors with CNS origin. Similar to all polyomaviruses, JCV encodes for several tumor antigens from a single transcript of early coding region via alternative splicing. There is little known regarding the characteristics of JCV induced tumors and impact of DNA damage induced by radiation on viral tumor antigen expression and growth of these cells. Here we analyzed the possible impact of ionizing radiation on transformed phenotype and tumor antigen expression by utilizing a mouse medulloblastoma cell line (BSB8) obtained from a mouse transgenic for JCV tumor antigens. Our results suggest that a small subset of BSB8 cells survives and shows radiation resistance. Further analysis of the transformed phenotype of radiation resistant BSB8 cells (BSB8-RR) have revealed that they are capable of forming significantly higher numbers and sizes of colonies under anchorage dependent and independent conditions with reduced viral tumor antigen expression. Moreover, BSB8-RR cells show an increased rate of double-strand DNA break repair by homologous recombination (HR). More interestingly, knockout studies of JCV tumor antigens by utilizing CRISPR/Cas9 gene editing reveal that unlike parental BSB8 cells, BSB8-RR cells are no longer required the expression of viral tumor antigens in order to maintain transformed phenotype.</p>","PeriodicalId":38987,"journal":{"name":"Genes and Cancer","volume":"9 3-4","pages":"130-141"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.18632/genesandcancer.174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36398055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}