Linked Life Data

9136987

Source:http://linkedlifedata.com/resource/pubmed/id/9136987

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1997-5-21
pubmed:abstractText
In recent work we showed that the EGF receptor (EGFr) was activated in tumor promoter treated mouse epidermis (Cell Growth & Differentiation, 6: 1447-1455, 1995). In the present study, we have investigated the possible role of other erbB family members in the process of tumor promotion. Both erbB2 and erbB3, but not erbB4, were expressed in cultured mouse keratinocytes and in mouse epidermis in vivo. In cultured mouse keratinocytes, EGF stimulated rapid tyrosine phosphorylation of erbB2 followed by a time-dependent degradation of erbB2 protein. Furthermore, an increase in erbB2:EGFr heterodimer formation was also induced by EGF. In contrast to the results with erbB2, EGF did not induce tyrosine phosphorylation, the degradation of erbB3, or erbB3:EGFr heterodimer formation in cultured keratinocytes. Further analyses revealed that c-src kinase activity was dramatically elevated in cultured mouse keratinocytes exposed to EGF. In mouse epidermis following multiple treatments with 12-O-tetradecanoylphorbol-13-acetate (TPA), the phosphotyrosine content of erbB2 was significantly elevated in a dose-dependent manner. Concomittantly, erbB2:EGFr heterodimer formation and c-src kinase activity were also elevated in TPA-treated epidermis. Structure-activity relationships with several phorbol ester analogs showed that the elevated phosphorylation of erbB2 in mouse epidermis followed closely with tumor promoting ability. Activation of erbB2 and c-src kinase were also observed in the epidermis of TGF alpha transgenic mice where expression of human TGF alpha was targeted to basal keratinocytes with the human K14 promoter. Collectively, the current data suggest that the activation of erbB2 in phorbol ester treated skin can be explained solely by a mechanism involving elevation of EGFr ligands and activation of the EGFr. In addition, activation of c-src may be an important downstream effector in mouse keratinocytes both in vivo and in vitro, following activation of the EGFr, erbB2, or both.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1435-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9136987-Animals, pubmed-meshheading:9136987-Carcinogens, pubmed-meshheading:9136987-Cells, Cultured, pubmed-meshheading:9136987-Enzyme Activation, pubmed-meshheading:9136987-Epidermal Growth Factor, pubmed-meshheading:9136987-Epidermis, pubmed-meshheading:9136987-Female, pubmed-meshheading:9136987-Keratinocytes, pubmed-meshheading:9136987-Mice, pubmed-meshheading:9136987-Mice, Transgenic, pubmed-meshheading:9136987-Phorbol Esters, pubmed-meshheading:9136987-Phosphorylation, pubmed-meshheading:9136987-Phosphotyrosine, pubmed-meshheading:9136987-Proto-Oncogene Proteins pp60(c-src), pubmed-meshheading:9136987-Receptor, Epidermal Growth Factor, pubmed-meshheading:9136987-Receptor, erbB-2, pubmed-meshheading:9136987-Receptor Aggregation, pubmed-meshheading:9136987-Signal Transduction, pubmed-meshheading:9136987-Skin Neoplasms, pubmed-meshheading:9136987-Transforming Growth Factor alpha
pubmed:year
1997
pubmed:articleTitle
Activation of erbB2 and c-src in phorbol ester-treated mouse epidermis: possible role in mouse skin tumor promotion.
pubmed:affiliation
The University of Texas, MD Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.