Linked Life Data

15482487

Source:http://linkedlifedata.com/resource/pubmed/id/15482487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-10-14
pubmed:abstractText
Keratin 10 (K10) is the major protein in the upper epidermis where it maintains keratinocyte integrity. Others have reported that K10 may act as a tumor suppressor upon ectopic expression in mice. Although K10(-/-) mice show significant epidermal hyperproliferation, accompanied by an activation of the mitogen-activated protein kinase (MAPK) pathway, they formed no spontaneous tumors. Here, we report that K10(-/-) mice treated with 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) developed far less papillomas than wild-type mice. BrdU(5-bromo-2'-deoxyuridine)-labeling revealed a strongly accelerated keratinocyte turnover in K10(-/-) epidermis suggesting an increased elimination of initiated keratinocytes at early stages of developing tumors. This is further supported by the absence of label-retaining cells 18 d after the pulse whereas in wild-type mice label-retaining cells were still present. The concomitant increase in K6, K16, and K17 in K10 null epidermis and the increased motility of keratinocytes is in agreement with the pliability versus resilience hypothesis, stating that K10 and K1 render cells more stable and static. The K10(-/-) knockout represent the first mouse model showing that loss of a keratin, a cytoskeletal protein, reduces tumor formation. This is probably caused by an accelerated turnover of keratinocytes, possibly mediated by activation of MAPK pathways.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
973-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Loss of keratin 10 leads to mitogen-activated protein kinase (MAPK) activation, increased keratinocyte turnover, and decreased tumor formation in mice.
pubmed:affiliation
Institut fuer Physiologische Chemie, Abteilung fuer Zellbiochemie, Bonner Forum Biomedizin and LIMES, Universitaetsklinikum Bonn, Bonn, Germany. j.reichelt@uni-bonn.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't