Linked Life Data

16473140

Source:http://linkedlifedata.com/resource/pubmed/id/16473140

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-2-13
pubmed:abstractText
Development of resistance to platinum compounds may involve not only overexpression of defence mechanisms but also alterations in cellular response to the drug-induced genotoxic stress. To investigate the cellular bases of response to platinum compounds, we examined the profile of gene expression of ovarian carcinoma cells exhibiting sensitivity (A2780) or resistance (A2780/BBR3464) to platinum compounds. Using display PCR, we found that acquisition of resistance to the multinuclear platinum complex BBR3464 was associated with modulation of several transcripts, including up-regulation of the major substrate of protein kinase C (PKC), the myristoylated alanine-rich C kinase substrate (MARCKS). This feature was associated with PKCalpha down-regulation. To explore the role of PKCalpha in cellular sensitivity to platinum compounds, resistant cells were transfected with a PKCalpha-containing vector. PKCalpha-overexpressing resistant cells exhibited a decrease in sensitivity to cisplatin, whereas no significant change in sensitivity to BBR3464 was observed. A number of approaches designed to modulate the function or expression of PKCalpha support that the isoenzyme may play a role in determining resistance only to cisplatin but not to BBR3464, which is known to activate a different pathway of cell response. In conclusion, in spite of PKCalpha down-regulation in our model, its regulatory function was not apparently implicated in the development of resistance to platinum compounds and the present results do not support a general role of PKCalpha as a determinant of the resistance status.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1763
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
93-100
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16473140-Cell Line, Tumor, pubmed-meshheading:16473140-Cisplatin, pubmed-meshheading:16473140-Drug Combinations, pubmed-meshheading:16473140-Drug Resistance, Neoplasm, pubmed-meshheading:16473140-Female, pubmed-meshheading:16473140-Gene Expression, pubmed-meshheading:16473140-Gene Expression Profiling, pubmed-meshheading:16473140-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16473140-Humans, pubmed-meshheading:16473140-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16473140-Isoenzymes, pubmed-meshheading:16473140-Membrane Proteins, pubmed-meshheading:16473140-Organoplatinum Compounds, pubmed-meshheading:16473140-Ovarian Neoplasms, pubmed-meshheading:16473140-Phenotype, pubmed-meshheading:16473140-Platinum Compounds, pubmed-meshheading:16473140-Protein Kinase C-alpha, pubmed-meshheading:16473140-Reproducibility of Results, pubmed-meshheading:16473140-Transfection
pubmed:year
2006
pubmed:articleTitle
Molecular alterations of cells resistant to platinum drugs: role of PKCalpha.
pubmed:affiliation
Istituto Nazionale per lo Studio e la Cura dei Tumori, via Venezian 1, 20133 Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't