142 research outputs found
Investigation into the molecular mechanism of the antiapoptotic functions of CTCF in breast cancer cells using a proteomics approach
Actualization of Evaluativity as a Qualitative Category in the Discourse of English Internet Film Review
Introduction. The article presents the results of the analysis aimed at identifying actualization methods of evaluativity as a qualitative category within the frames of the evaluative subgenres of expert and professional film reviews. The author assumes that evaluativity serves as a method of explicating subject's attitude towards the content of the film. The relevance of the study is determined by a lack of research dedicated to the analysis of the methods expressing author’s position within the evaluative genre of internet film review. The interconnection of evaluativity category, subject factor and modus as a method of explicating subjective meanings of the statement are analyzed.Methodology and sources. The methodology of the research is based on the classification of evaluative meanings developed by N. Arutyunova. The research methodology includes PoS tagging of the texts, identification of evaluative units including qualitative adjectives and adverbs, as well as description and comparison of leading evaluation types that actualize author's position. The methodology was studied using the example of a text corpora consisting of expert and professional film reviews extracted from the web archive of the journal of Film Criticism and the website metacritic.com.Results and discussion. With the implementation of PoS tagging and quantitative method of analysis leading evaluation categories within the corpora of the professional and expert film reviews were described and compared. The results have shown that the leading type of evaluation within the frames of the referred evaluative subgenres is represented by the emotional evaluation category. The results have also indicated that the leading evaluation types of expert evaluative discourse include prescriptive and ethical evaluation, whereas professional evaluative discourse is characterized by the prevalence of generalized evaluative units.Conclusion. The analysis allowed the author to conclude that the referred genres are characterized mainly by increased expressivity and emotiveness. However, author’s position actualization in the discourse of expert film review implicates detailed analysis of structural contents of the presented norms, as well as content of the film, whereas the discourse of professional film review is characterized by increased generalization tendency, which implicates low degree of authors’ competency
Expressing the Author's Position in the English-Language Network Film Review
Introduction. The article presents the results of the analysis of the author’s position verbalization methods in the English online professional film review addressed to the mainstream audience. The authors proceed from the position that the methods of subject verbalization are determined by functional characteristics of discourse. The relevance of the study is due to the interest of modern linguistics in the study of the subject factor in “personal” types of discourse. The paper considers the factor of the subject in the discourse, defines the concepts of authorization and its nomination, analyzes the role of identifying categories of subjective modality and describing prevalent evaluation types in the study of the author's position in evaluative genres.Methodology and sources. Research methodology is based on the approaches to classification of modus and evaluation types developed by N.D. Arutyunova. The methodology of describing the author's position in evaluative genres is proposed, which boils down to the following steps: identifying the leading linguistic means of self-nomination; displaying main genre-typical patterns of subject modality (modus types); describing evaluation semantics specificity and linguistic means of dominant evaluative meanings verbalization. The study was conducted on the material of the corpus of texts selected on the English-language portal metacritic.com which includes 50 professional film reviews addressed to a wide audience (39,765 words in length).Results and discussion. Based on the methods of quantitative and contextual analysis the distribution of modus types verbalized by “subject-predicate” models with personal subject-representing pronouns was carried out; the distribution of personal and possessive pronouns as the main method of self-nomination in the discourse of the network English-language professional film review was revealed; on the basis of the analysis of the semantics of evaluative adjectives of the corpus, the types of evaluative meanings in the genre under study were identified. The leading methods of discourse subject nomination were shown to involve the 1-st person pl. inclusive pronoun, which indicates the author’s intention to establish a connection with the reader and to increase the manipulative potential of the text. The main types of evaluative meanings verbalized by the corpora adjectives were identified, which are emotional, intellectual, aesthetic and regulatory types.Conclusion. The conducted research allowed us to conclude that the specificity of the expression of the author's position in professional network film review is reduced to the following characteristics: the dominant nature of the perceptual mode and the mental mode of knowledge in the field of subjective modality of texts; the predominance of first-person plural pronouns in an inclusive meaning as a means of self-nomination of the subject discourse and the dominance of partial-evaluative meanings over general-evaluative ones. The predominance of emotional-psychological and intellectual-psychological types of evaluation indicates the author's intention to express an individualized subjective-emotional opinion about the evaluated object
Regulation of the apoptotic genes in breast cancer cells by the transcription factor CTCF
CTCF is a highly conserved and ubiquitous transcription factor with versatile functions. We previously demonstrated that elevated protein levels of CTCF in breast cancer cells were associated with the specific anti-apoptotic function of CTCF. We used proteomics and microarray approaches to identify regulatory targets of CTCF specific for breast cancer cells. Among the CTCF identified targets were proteins involved in the control of apoptosis. A proapoptotic protein, Bax, negatively regulated by CTCF, was chosen for further investigation. Repression of the human Bax gene at the transcriptional level by CTCF in breast cancer cells was confirmed by real-time PCR. Two CTCF binding sites within the Bax promoter were identified by electrophoretic mobility shift assay and footprinting. In reporter assays, the Bax-luciferase reporter construct, containing CTCF-binding sites, was negatively regulated by CTCF. In vivo, CTCF occupied its binding sites in breast cancer cells and tissues, as confirmed by chromatin immunoprecipitation assay. Our findings suggest a possible mechanism of the specific CTCF anti-apoptotic function in breast cancer cells whereby CTCF is bound to the Bax promoter, resulting in repression of Bax and inhibition of apoptosis; depletion of CTCF leads to activation of Bax and apoptotic death. CTCF binding sites in the Bax promoter are unmethylated in all cells and tissues inspected. Therefore, specific CTCF interaction with the Bax promoter in breast cancer cells, and the functional outcome, may depend on a combination of epigenetic factors characteristic for these cells. Interestingly, CTCF appears to be a negative regulator of other proapoptotic genes (for example, Fas, Apaf-1, TP531NP1). Conversely, stimulating effects of CTCF on the anti-apoptotic genes (Bcl-2, Bag-3) have been observed. Taken together, these findings suggest that specific mechanisms have evolved in breast cancer cells to protect them from apoptosis; regulation of apoptotic genes by CTCF appears to be one of the resistance strategies
Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells
BORIS (CTCFL) is the paralog of CTCF (CCCTC-binding factor; NM_006565), a ubiquitously expressed DNA-binding protein with diverse roles in gene expression and chromatin organisation. BORIS and CTCF have virtually identical zinc finger domains, yet display major differences in their respective C- and N-terminal regions. Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a “cancer-testis” antigen. However, the expression pattern of BORIS is both a significant and unresolved question in the field of DNA binding proteins. Here, we identify BORIS in the cytoplasm and nucleus of a wide range of normal and cancer cells. We compare the localization of CTCF and BORIS in the nucleus and demonstrate enrichment of BORIS within the nucleolus, inside the nucleolin core structure and adjacent to fibrillarin in the dense fibrillar component. In contrast, CTCF is not enriched in the nucleolus. Live imaging of cells transiently transfected with GFP tagged BORIS confirmed the nucleolar accumulation of BORIS. While BORIS transcript levels are low compared to CTCF, its protein levels are readily detectable. These findings show that BORIS expression is more widespread than previously believed, and suggest a role for BORIS in nucleolar function
BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours
BORIS (for brother of the regulator of imprinted sites), a paralogue of the transcription factor, CTCF, is a novel member of the cancer-testis antigen family. The aims of the present study were as follows: (1) to investigate BORIS expression in breast cells and tumours using immunohistochemical staining, western and real-time RT–PCR analyses and (2) assess potential correlation between BORIS levels in tumours with clinical/pathological parameters. BORIS was detected in all 18 inspected breast cell lines, but not in a primary normal breast cell culture. In 70.7% (41 of 58 cases) BORIS was observed in breast tumours. High levels of BORIS correlated with high levels of progesterone receptor (PR) and oestrogen receptor (ER). The link between BORIS and PR/ER was further confirmed by the ability of BORIS to activate the promoters of the PR and ER genes in the reporter assays. Detection of BORIS in a high proportion of breast cancer patients implies potential practical applications of BORIS as a molecular biomarker of breast cancer. This may be important for diagnosis of the condition and for the therapeutic use of BORIS. The ability of BORIS to activate promoters of the RP and ER genes points towards possible involvement of BORIS in the establishment, progression and maintenance of breast tumours
Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer
The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour tissues and matched non-tumour tissues from 22 breast and 42 colorectal cancer patients as well as peripheral blood samples obtained from colorectal cancer patients [SEARCH (n=case 192, controls 96)], breast cancer patients [ABC (n=case 364, controls 96)] and the European Prospective Investigation of Cancer [EPIC-Norfolk (n=breast 228, colorectal 225, controls 895)] were analysed. The EPIC samples were collected 2–5 years prior to diagnosis of breast or colorectal cancer. IGF2 DMR0 methylation levels in tumours were lower than matched non-tumour tissue. Hypomethylation of DMR0 was detected in breast (33%) and colorectal (80%) tumour tissues with a higher frequency than LOI indicating that methylation levels are a better indicator of cancer than LOI. In the EPIC population, the prevalence of IGF2 DMR0 hypomethylation was 9.5% and this correlated with increased age not cancer risk. Thus, IGF2 DMR0 hypomethylation occurs as an acquired tissue-specific somatic event rather than a constitutive innate epimutation. These results indicate that IGF2 DMR0 hypomethylation has diagnostic potential for colon cancer rather than value as a surrogate biomarker for constitutive LOI
- …
