Linked Life Data

19808857

Source:http://linkedlifedata.com/resource/pubmed/id/19808857

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-12-16
pubmed:abstractText
The association between inflammation and tumorigenesis is well recognized. Mitogen-activated protein kinase-activated protein kinase-2 (MK2) is known to play a pivotal role in inflammatory processes. Here, we studied the effect of MK2-deficiency and tumor necrosis factor (TNF)-alpha-deficiency on skin tumor development in mice using the two-stage chemical carcinogenesis model. We found that MK2(-/-) mice developed significantly fewer skin tumors compared with both TNF-alpha(-/-) and wild-type mice when induced by initiation with 7,12-dimethylbenz[a]anthracene (DMBA) and by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). The TPA-induced inflammatory response was reduced in both, TNF-alpha(-/-) mice and MK2(-/-) mice, but most pronounced in TNF-alpha(-/-) mice, indicating that a reduced inflammatory response was not the only explanation for the inhibited tumorigenesis seen in MK2(-/-) mice. Interestingly, increased numbers of apoptotic cells were detected in the epidermis of MK2(-/-) mice compared with TNF-alpha(-/-) and wild-type mice, suggesting an additional role of MK2 in the regulation of apoptosis. This was further supported by: (i) increased levels of the tumor suppressor protein p53 in MK2(-/-) mice after DMBA/TPA treatment compared with controls, (ii) reduced phosphorylation (activation) of the negative p53 regulator, murine double minute 2 in MK2(-)(/-) mouse keratinocytes in vitro and (iii) a significant decrease in the DMBA/TPA induced apoptosis in cultured MK2(-/-) keratinocytes transfected with p53 small interfering RNA. Taken together, these findings demonstrate a dual role of MK2 in the early stages of tumor promotion through regulation of both the inflammatory response and apoptosis of DNA-damaged cells. These results also identify MK2 as a putative target for future skin carcinoma therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2100-8
pubmed:meshHeading
pubmed-meshheading:19808857-Animals, pubmed-meshheading:19808857-Apoptosis, pubmed-meshheading:19808857-DNA Damage, pubmed-meshheading:19808857-Disease Progression, pubmed-meshheading:19808857-Gene Expression Regulation, Neoplastic, pubmed-meshheading:19808857-Inflammation, pubmed-meshheading:19808857-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:19808857-Keratinocytes, pubmed-meshheading:19808857-Mice, pubmed-meshheading:19808857-Mice, Transgenic, pubmed-meshheading:19808857-Phosphorylation, pubmed-meshheading:19808857-Protein-Serine-Threonine Kinases, pubmed-meshheading:19808857-RNA, Small Interfering, pubmed-meshheading:19808857-Skin Neoplasms, pubmed-meshheading:19808857-Tetradecanoylphorbol Acetate, pubmed-meshheading:19808857-Tumor Necrosis Factor-alpha, pubmed-meshheading:19808857-Tumor Suppressor Protein p53
pubmed:year
2009
pubmed:articleTitle
MK2 regulates the early stages of skin tumor promotion.
pubmed:affiliation
Department of Dermatology, Aarhus University Hospital, P.P. Oerumsgade 11, 8000 Aarhus, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't