uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Protein kinase Cdelta supports survival of MDA-MB-231 breast cancer cells by suppressing the ERK1/2 pathway
Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, and Malmö University Hospital, Sweden.
Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, and Malmö University Hospital, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Ludwig Institute for Cancer Research.
Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, and Malmö University Hospital, Sweden.
2009 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 284, no 48, 33456-33465 p.Article in journal (Refereed) Published
Abstract [en]

Mechanisms that mediate apoptosis resistance are attractive therapeutic targets for cancer. Protein kinase Cdelta (PKCdelta) is considered a pro-apoptotic factor in many cell types. In breast cancer, however, it has shown both pro-survival and pro-apoptotic effects. Here, we report for the first time that down-regulation of PKCdelta per se leads to apoptosis of MDA-MB-231 cells. Inhibition of MEK1/2 by either PD98059 or U0126 suppressed the induction of apoptosis of PKCdelta-depleted MDA-MB-231 cells but did not support survival of MCF-7 or MDA-MB-468 cells. Basal ERK1/2 phosphorylation was substantially higher in MDA-MB-231 cells than in the other cell lines. PKCdelta depletion led to even higher ERK1/2 phosphorylation levels and also to lower expression levels of the ERK1/2 phosphatase MKP3. Depletion of MKP3 led to apoptosis and higher levels of ERK1/2 phosphorylation, suggesting that this may be a mechanism mediating the effect of PKCdelta down-regulation. However, PKCdelta silencing also induced increased MEK1/2 phosphorylation, indicating that PKCdelta regulates ERK1/2 phosphorylation both upstream and downstream. Moreover, PKCdelta silencing led to increased levels of the E3 ubiquitin ligase Nedd4, which is a potential regulator of MKP3, because down-regulation led to increased MKP3 levels. Our results highlight PKCdelta as a potential target for therapy of breast cancers with high activity of the ERK1/2 pathway.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology, Inc. , 2009. Vol. 284, no 48, 33456-33465 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-112886DOI: 10.1074/jbc.M109.036186ISI: 000272028500052PubMedID: 19833733OAI: oai:DiVA.org:uu-112886DiVA: diva2:288707
Available from: 2010-01-21 Created: 2010-01-21 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Journal of Biological Chemistry
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 406 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf