Linked Life Data

15640620

Source:http://linkedlifedata.com/resource/pubmed/id/15640620

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-2-15
pubmed:abstractText
Metastatic cervical cancer remains a clinical problem. The development of more efficient treatment modalities and the optimal use of chemo- and radiotherapy require better understanding of their impact on regulation of cell survival and apoptosis, but the issue is insufficiently explored. Human papillomavirus (HPV) E6 protein is present in nearly all cervical cancers, targeting the p53 tumor suppressor protein for degradation. We studied the role of p53 in mediating the cytotoxic effects of 31 chemotherapy compounds. SiHa cervical cancer cells, carrying wild type (wt) p53 and HPV16 genome, were stably transfected with dominant negative p53 (DDp53) or ectopic HPV16 E6 in order to inhibit p53 function. The effects of chemotherapy drugs in these cells were compared to the effects in cells retaining endogenous residual p53 activity. Twenty-ight out of 31 drugs reduced the amount of E6 mRNA, but only some induced marked p53 activation. In clonogenic cell survival experiments, the presence of DDp53 and ectopic E6 either increased or decreased cytotoxicity, depending on the drug. The decrease of E6 mRNA was necessary, but not sufficient event in the p53 activation by chemotherapy. The impact of p53 on clonogenic cell survival varied between 0-60%, indicating that p53 plays an important, but not crucial role in response to chemotherapy. The finding that chemosensitivity varies depending on the p53 status may have clinical implications, since early stage cervical cancer cells usually carry wt p53, whereas p53 mutations are frequently found in advanced disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-4047
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1177-83
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
The cytotoxicity of chemotherapy drugs varies in cervical cancer cells depending on the p53 status.
pubmed:affiliation
Medicity Research Laboratory, University of Turku, Turku, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't