Source:http://linkedlifedata.com/resource/pubmed/id/19417139
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2009-5-18
|
| pubmed:abstractText |
Acquired resistance to protein kinase C (PKC) modulators may explain the failure of clinical trials in patients with cancer. Herein, we established a human colon cancer cell line resistant to PEP005, a drug that inhibits PKCalpha and activates PKCdelta. Colo205-R cells, selected by stepwise exposure to PEP005, were >300-fold more resistant to PEP005 than parental Colo205-S cells and were cross-resistant to phorbol 12-myristate 13-acetate, bryostatin, bistratene A, and staurosporine. No PKCalpha or PKCdelta mutation was detected in Colo205-S and Colo205-R cells. Changes in Colo205-R cells were reminiscent of the epithelial-to-mesenchymal transition (EMT) phenotype. Accordingly, Colo205-R cells were more invasive than Colo205-S in Matrigel assays and in mouse xenografts. We also found an increased mRNA expression of several EMT genes, such as those encoding for transforming growth factor-beta and vimentin, along with a decreased mRNA expression of genes involved in epithelial differentiation, such as CDH1 (E-cadherin), CLDN4 (claudin 4), S100A4, and MUC1, in Colo205-R compared with Colo205-S cells in vitro and in vivo. Interestingly, high expression of ET-1 was shown in Colo205-R cells and correlated with low sensitivity to PEP005 and staurosporine in a panel of 10 human cancer cell lines. Inhibition of the ET-1 receptor ETR-A with bosentan restored the antiproliferative effects of PEP005 in Colo205-R cells and decreased the invasive properties of this cell line. Exogenous exposure to ET-1 and silencing ET-1 expression using small interfering RNA modulated cell signaling in Colo205-S and Colo205-R. In summary, acquired resistance to PEP005 was associated with expression of EMT markers and activates the ET-1/ETR-A cell signaling.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-ingenyl angelate,
http://linkedlifedata.com/resource/pubmed/chemical/Diterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-delta,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
1538-7445
|
| pubmed:author |
pubmed-author:Astorgues-XerriLucileL,
pubmed-author:BenhadjiKarim AKA,
pubmed-author:BiecheIvanI,
pubmed-author:BousquetGuilhemG,
pubmed-author:CvitkovicEstebanE,
pubmed-author:FaivreSandrineS,
pubmed-author:LokiecFrançoisF,
pubmed-author:PhillipsEdelmiraE,
pubmed-author:RaymondEricE,
pubmed-author:SerovaMariaM,
pubmed-author:ShanGuangG,
pubmed-author:VarnaMarianaM,
pubmed-author:VidaudMichelM,
pubmed-author:WeillSophieS
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
69
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
4260-9
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:19417139-Animals,
pubmed-meshheading:19417139-Breast Neoplasms,
pubmed-meshheading:19417139-Cell Differentiation,
pubmed-meshheading:19417139-Cell Division,
pubmed-meshheading:19417139-Cell Line, Tumor,
pubmed-meshheading:19417139-Cell Survival,
pubmed-meshheading:19417139-Colonic Neoplasms,
pubmed-meshheading:19417139-Diterpenes,
pubmed-meshheading:19417139-Epithelial Cells,
pubmed-meshheading:19417139-Exons,
pubmed-meshheading:19417139-Female,
pubmed-meshheading:19417139-Humans,
pubmed-meshheading:19417139-Matrix Metalloproteinases,
pubmed-meshheading:19417139-Mesoderm,
pubmed-meshheading:19417139-Mice,
pubmed-meshheading:19417139-Mice, Nude,
pubmed-meshheading:19417139-Neoplasm Invasiveness,
pubmed-meshheading:19417139-Ovarian Neoplasms,
pubmed-meshheading:19417139-Protein Kinase C-alpha,
pubmed-meshheading:19417139-Protein Kinase C-delta,
pubmed-meshheading:19417139-RNA, Messenger,
pubmed-meshheading:19417139-RNA, Small Interfering,
pubmed-meshheading:19417139-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19417139-Transplantation, Heterologous
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Epithelial-to-mesenchymal transition and resistance to ingenol 3-angelate, a novel protein kinase C modulator, in colon cancer cells.
|
| pubmed:affiliation |
Institut National de la Sante et de la Recherche Medicale U728, RayLab, and Department of Medical Oncology, Beaujon and Saint-Louis University Hospital (AP-HP-Paris 7 Diderot), Clichy, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|