Severity: Warning
Message: file_get_contents(https://...@pubfacts.com&api_key=b8daa3ad693db53b1410957c26c9a51b4908&a=1): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 176
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 176
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 250
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 1034
Function: getPubMedXML
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3152
Function: GetPubMedArticleOutput_2016
File: /var/www/html/application/controllers/Detail.php
Line: 575
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 489
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Background: Recombinant human erythropoietin (EPO) is the leading biotechnology engineered hormone for treatment of anaemia associated with chronic conditions including kidney failure and cancer. The finding of EPO receptors on cancer cells has raised the concern that in addition to its action in erythropoiesis, EPO may promote tumour cell growth. We questioned whether EPO-induced signalling and consequent malignant cell manifestation is mediated by polyADP-ribosylation.
Methods: Erythropoietin-mediated PARP (polyADP-ribose polymerase-1) activation, gene expression and core histone H4 acetylation were examined in UT7 cells, using western blot analysis, RT-PCR and immunofluorescence. Erythropoietin-driven migration of the human breast epithelial cell line MDA-MB-435 was determined by the scratch assay and in migration chambers.
Results: We have found that EPO treatment induced PARP activation. Moreover, EPO-driven c-fos and Egr-1 gene expression as well as histone H4 acetylation were mediated via polyADP-ribosylation. Erythropoietin-induced cell migration was blocked by the PARP inhibitor, ABT-888, indicating an essential role for polyADP-ribosylation in this process.
Conclusions: We have identified a novel pathway by which EPO-induced gene expression and breast cancer cell migration are regulated by polyADP-ribosylation. This study introduces new possibilities regarding EPO treatment for cancer-associated anaemia where combining systemic EPO treatment with targeted administration of PARP inhibitors to the tumour may allow safe treatment with EPO, minimising its possible undesirable proliferative effects on the tumour.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494439 | PMC |
http://dx.doi.org/10.1038/bjc.2012.395 | DOI Listing |
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