Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
Filter
  • DKFZ Publication Database  (4)
  • BREAST-CANCER  (4)
Collection
  • DKFZ Publication Database  (4)
  • 1
    Keywords: CANCER ; EXPRESSION ; INVASION ; DIFFERENTIATION ; BREAST-CANCER ; COLORECTAL-CANCER ; STEM-CELLS ; SOMATIC MUTATIONS ; ENHANCER-OF-ZESTE-HOMOLOG-2 GENE ; HISTONE METHYLTRANSFERASE ; METHYLTRANSFERASE GENE EZH2 ; NUMBERS
    Abstract: The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi) mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer
    Type of Publication: Journal article published
    PubMed ID: 21765901
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: BREAST-CANCER ; CANCER-CELLS ; CERVICAL-CARCINOMA CELLS ; HUMAN KERATINOCYTES ; HUMAN-PAPILLOMAVIRUS TYPE-16 ; E7 ONCOPROTEIN ; E6 ONCOPROTEIN ; RNA INTERFERENCE ; EXTRACELLULAR VESICLES ; CIRCULATING MICRORNA
    Abstract: Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR-186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143-3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on miRNA levels are mainly not dependent on p53 and similarly observed in HPV16-positive SiHa cells. The E6/E7-regulated miRNAs are enriched for species involved in the control of cell proliferation, senescence and apoptosis, suggesting that they contribute to the growth of HPV-positive cancer cells. Consistently, we show that sustained E6/E7 expression is required to maintain the intracellular levels of members of the miR-17 similar to 92 cluster, which reduce expression of the anti-proliferative p21 gene in HPV-positive cancer cells. In exosomes secreted by HeLa cells, a distinct seven-miRNA-signature was identified among the most abundant miRNAs, with significant downregulation of let-7d-5p, miR-20a-5p, miR-378a-3p, miR-423-3p, miR-7-5p, miR-92a-3p and upregulation of miR-21-5p, upon E6/E7 silencing. Several of the E6/E7-dependent exosomal miRNAs have also been linked to the control of cell proliferation and apoptosis. This study represents the first global analysis of intracellular and exosomal miRNAs and shows that viral oncogene expression affects the abundance of multiple miRNAs likely contributing to the E6/E7-dependent growth of HPV-positive cancer cells.
    Type of Publication: Journal article published
    PubMed ID: 25760330
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: IN-VITRO ; carcinoma ; INHIBITION ; MODEL ; PROTEIN ; SUPPRESSION ; BREAST-CANCER ; TUMOR PROGRESSION ; OVEREXPRESSION ; CYCLE REGULATOR
    Abstract: Background: The B-cell translocation gene 2 (BTG2) is considered to act as a tumour-suppressor gene because of its antiproliferative and antimigratory activities. Higher levels of BTG2 expression in tumour cells have been linked to a better clinical outcome for several cancer entities. Here, we investigated the expression and function of BTG2 in bladder cancer. Methods: The expression of BTG2 in bladder cancer cells was silenced by RNA interference. Cell motility was investigated by wound healing and Boyden chamber assays. The protein expression of BTG2 in bladder cancer was studied by immunohistochemistry. Results: We observed that targeted suppression of BTG2 by RNA interference did not result in growth stimulation but led to a substantial inhibition of bladder cancer cell motility. Tissue microarray analyses of bladder cancer cystectomy specimens revealed that higher BTG2 expression levels within the tumours correlated strongly with a decreased cancer-specific survival for bladder cancer patients. Conclusion: These results indicate that endogenous BTG2 expression contributes to the migratory potential of bladder cancer cells. Moreover, high levels of BTG2 in bladder cancers are linked to decreased cancer-specific survival. These findings question the conception that BTG2 generally acts as a tumour suppressor and typically represents a favourable clinical marker for cancer patients.
    Type of Publication: Journal article published
    PubMed ID: 23299537
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; proliferation ; tumor ; TUMOR-CELLS ; CELL ; CELL-PROLIFERATION ; Germany ; human ; IN-VIVO ; VIVO ; GENE ; GENES ; PROTEIN ; PROTEINS ; RNA ; RELEASE ; ACTIVATION ; cell cycle ; CELL-CYCLE ; E7 ; papillomavirus ; BREAST-CANCER ; TARGET ; virus ; LESIONS ; PROGRESSION ; resistance ; cervical cancer ; CERVICAL-CANCER ; PROSTATE-CANCER ; human papillomavirus ; TYPE-16 ; CANCER-CELLS ; HPV ; E6 ; ONCOGENE ; HPV16 ; HUMAN-PAPILLOMAVIRUS ; PHENOTYPE ; ONCOPROTEIN ; METHYLTRANSFERASE ACTIVITY ; E6 ONCOPROTEIN ; ONCOLOGY ; ENHANCER ; RE ; INTERFERENCE ; RNA INTERFERENCE ; LEVEL ; USA ; oncogenes ; cancer research ; viral ; transformed cell ; GROUP PROTEIN EZH2 ; POLYCOMB REPRESSION
    Abstract: The malignant phenotype of human papillomavirus (HPV)-positive cancer cells is maintained by the activity of the viral E6 and E7 genes. Here, we identified the polycomb group gene enhancer of zeste homologue 2 (EZH2) as a novel downstream target for the viral oncogenes in HPV transformed cells. EZH2 expression was activated by HPV16 E7 at the transcriptional level via E7-mediated release of E2F from pocket proteins. RNA interference analyses showed that continuous EZH2 expression is required for the proliferation of HPV-positive tumor cells by stimulating cell cycle progression at the G(1)-S boundary. In addition to its growth-promoting activity, EZH2 also contributed to the apoptotic resistance of cervical cancer cells. Furthermore, we found that HPV-positive dysplastic and tumorigenic cervical lesions were characterized by high levels of EZH2 protein in vivo. We conclude that the E7 target gene EZH2 is a major determinant for the proliferation of HPV-positive cancer cells and contributes to their apoptotic resistance. Moreover, EZH2 may serve as a novel therapeutic target for the treatment of cervical cancer. [Cancer Res 2008;68(23):9964-72]
    Type of Publication: Journal article published
    PubMed ID: 19047178
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...