Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • POSITIVE CANCER-CELLS  (5)
  • 1
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; tumor ; carcinoma ; CELL ; Germany ; human ; INHIBITION ; GENE ; PROTEIN ; TISSUE ; CARCINOGENESIS ; DOWN-REGULATION ; E7 ; papillomavirus ; TARGET ; virus ; ELEMENT ; LESIONS ; PROMOTER ; cervical cancer ; CERVICAL-CANCER ; p53 ; GROWTH-INHIBITION ; human papillomavirus ; CANCER-CELLS ; HPV ; E6 ; ONCOGENE ; HPV16 ; HUMAN-PAPILLOMAVIRUS ; CARCINOMAS ; POSITIVE CANCER-CELLS ; TRANSLOCATION ; OVEREXPRESSION ; REPRESSION ; RETINOIC ACID ; E6 ONCOPROTEIN ; TUMOR-SUPPRESSOR ; papillomaviruses ; LEVEL ; tumor suppressor gene ; EPITHELIUM ; USA ; oncogenes ; B-CELL ; HUMAN PAPILLOMAVIRUSES ; tumor suppressor genes ; NOV ; tumor suppressor ; Luciferase reporter ; BTG2 ; cervical cancers ; viral carcinogenesis
    Abstract: Human papillomavirus (HPV)-induced carcinogenesis is critically dependent on the activities of the viral E6 and E7 oncogenes. Here, we demonstrate that expression of the putative tumor suppressor gene B-cell translocation gene-2 (BTG2) is reinduced in HPV16- and HPV18-positive cancer cells on silencing of viral oncogene expression, indicating that BTG2 is repressed by oncogenic HPVs. Inhibition of BTG2 expression was mediated by the HPV E6 oncogene and occurred in a p53-dependent manner. Luciferase reporter gene analyses revealed that BTG2 repression takes place at the transcriptional level and is dependent on the integrity of the major p53-response element within the BTG2 promoter. Ectopic expression of BTG2 acted antiproliferative in cervical cancer cells. Tissue specimens commonly exhibited reduced BTG2 protein levels in HPV-positive high-grade lesions (CIN2/3) and cervical carcinomas, when compared with normal cervical epithelium. These findings identify the antiproliferative BTG2 gene as a novel cellular target blocked by the HPV E6 oncoprotein. (C) 2009 UICC
    Type of Publication: Journal article published
    PubMed ID: 19551855
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    facet.materialart.
    facet.materialart.
    International Journal of Cancer 129 (6), 1289-1299 
    Keywords: HEPATOCELLULAR-CARCINOMA ; cervical cancer ; HPV ; CERVICAL-CARCINOMA CELLS ; POSITIVE CANCER-CELLS ; intraepithelial neoplasia ; vaccination ; HUMAN-PAPILLOMAVIRUS TYPE-16 ; EPSTEIN-BARR-VIRUS ; HEPATITIS-C VIRUS ; HCV ; HIV ; EBV ; liver cancer ; EPIGENETICS ; miRNA ; HBV ; tumor viruses ; HTLV-1 ; KAPOSI-SARCOMA ; LYTIC CYCLE REPLICATION ; VIRAL E6 ONCOPROTEIN ; virus detection
    Abstract: After a long period of scepticism and disbelief, tumor viruses are today recognized as a significant cancer risk factor for humans. Much has been learned about the viral transforming mechanisms and prophylactic vaccines have been developed against 2 major tumor viruses, HBV and HPV. Yet, many important issues of tumor virology remain unresolved and exciting new ones are emerging from recent discoveries. They define future research directions for the field and include (i) novel strategies for tumor virus hunting, (ii) tumor viruses as experimental tools to study human carcinogenesis, (iii) the interplay between viruses and the world of small noncoding RNAs, (iv) epigenetic interactions between tumor viruses and the host cell, (v) the role of virus/virus interactions for viral carcinogenesis and (vi) novel strategies for prevention and therapy of virus-associated cancers. These topics are discussed by summarizing recent developments, pointing out unresolved issues and suggesting possible strategies for their solution
    Type of Publication: Journal article published
    PubMed ID: 21445966
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: APOPTOSIS ; PROTEIN ; INDUCTION ; ASSOCIATION ; CERVICAL-CANCER ; p53 ; POSITIVE CANCER-CELLS ; NUCLEAR-LOCALIZATION ; E6-MEDIATED DEGRADATION ; AGGRESOMES
    Abstract: Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer and other malignancies in humans. The HPV E6 oncoprotein is considered to be an attractive therapeutic target since its inhibition can lead to the apoptotic cell death of HPV-positive cancer cells. The HPV type 16 (HPV16) E6-binding peptide pep11, and variants thereof, induce cell death specifically in HPV16-positive cancer cells. Although they do not encompass the LxxLL binding motif found in cellular HPV16 E6 interaction partners, such as E6AP, the pep11 variants strongly bind to HPV16 E6 by contacting the recently identified E6AP binding pocket. Thus, these peptides can serve as prototype E6-inhibitory molecules which target the E6AP pocket. We here analyzed their intracellular interaction with HPV16 E6. By comprehensive intracellular binding studies and GST pull-down assays, we show that E6-binding competent pep11 variants induce the formation of a trimeric complex, consisting of pep11, HPV16 E6 and p53. These findings indicate that peptides, which do not contain the LxxLL motif, can reshape E6 to enable its interaction with p53. The formation of the trimeric HPV16 E6 / peptide / p53 complex was associated with an increase of endogenous HPV16 E6 protein amounts. Yet, total cellular p53 amounts were also increased, indicating that the E6 / E6AP-mediated degradation of p53 is blocked. These findings suggest that inhibition of oncogenic activities by targeting the E6AP pocket on HPV16 E6 could be a strategy for therapeutic intervention.
    Type of Publication: Journal article published
    PubMed ID: 26151636
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: IN-VITRO ; PROSTATE-CANCER ; POSITIVE CANCER-CELLS ; OXIDATIVE STRESS ; TRANSCRIPTIONAL REGULATION ; RNA INTERFERENCE ; NUCLEAR-LOCALIZATION SIGNAL ; HIV-1 INTEGRASE ; INTEGRASE INTERACTOR LEDGF/P75 ; DNA-END RESECTION
    Abstract: The expression of the human papillomavirus (HPV) E6/E7 oncogenes is crucial for HPV-induced malignant cell transformation. The identification of cellular targets attacked by the HPV oncogenes is critical for our understanding of the molecular mechanisms of HPV-associated carcinogenesis and may open novel therapeutic opportunities. Here, we identify the Lens Epithelial-Derived Growth Factor (LEDGF) gene as a novel cellular target gene for the HPV oncogenes. Elevated LEDGF expression has been recently linked to human carcinogenesis and can protect tumor cells towards different forms of cellular stress. We show that intracellular LEDGF mRNA and protein levels in HPV-positive cancer cells are critically dependent on the maintenance of viral oncogene expression. Ectopic E6/E7 expression stimulates LEDGF transcription in primary keratinocytes, at least in part via activation of the LEDGF promoter. Repression of endogenous LEDGF expression by RNA interference results in an increased sensitivity of HPV-positive cancer cells towards genotoxic agents. Immunohistochemical analyses of cervical tissue specimens reveal a highly significant increase of LEDGF protein levels in HPV-positive lesions compared to histologically normal cervical epithelium. Taken together, these results indicate that the E6/E7-dependent maintenance of intracellular LEDGF expression is critical for protecting HPV-positive cancer cells against various forms of cellular stress, including DNA damage. This could support tumor cell survival and contribute to the therapeutic resistance of cervical cancers towards genotoxic treatment strategies in the clinic.
    Type of Publication: Journal article published
    PubMed ID: 24604027
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: APOPTOSIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; CELL ; Germany ; INHIBITION ; THERAPY ; PROTEIN ; BINDING ; papillomavirus ; FORM ; IDENTIFICATION ; genetics ; cervical cancer ; CERVICAL-CANCER ; p53 ; human papillomavirus ; CERVICAL-CARCINOMA CELLS ; E6 ; DEGRADATION ; POSITIVE CANCER-CELLS ; AFFINITY ; VARIANT ; THERAPIES ; cancer therapy ; LIBRARIES ; TYPE-16 E6 ; development ; P53 ACTIVITY ; oncogenes ; E6-AP
    Abstract: Specific types of human papillomaviruses (HPVs) cause cervical cancer. The viral E6 oncogene is a critical factor for maintaining the malignant phenotype of HPV-positive tumour cells. By yeast two-hybrid screening of a randomised peptide expression library, we isolated linear short peptides, which specifically bind to the HPV16 E6 oncoprotein. Sequence alignments and mutational analyses of the peptides identified a hitherto undiscovered E6-binding motif. Intracellular expression of a peptide containing the novel E6-binding motif resulted in inhibition of colony formation capacity, specifically of HPV16-positive cancer cells. A solubility-optimised variant of the peptide was created, which binds to HPV16 E6 with high affinity. Its intracellular expression efficiently induced apoptosis in HPV16-positive cancer cells. This was linked to restoration of intracellular p53 activities. Thus, this newly identified E6-binding motif could form a novel basis for the development of rational strategies for the treatment of HPV16-positive preneoplastic and neoplastic lesions
    Type of Publication: Journal article published
    PubMed ID: 19099279
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...