Linked Life Data

19060248

Source:http://linkedlifedata.com/resource/pubmed/id/19060248

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-5
pubmed:abstractText
The Src family tyrosine kinases are key modulators of cancer cell invasion and metastasis and a number of Src kinase inhibitors are currently in clinical development for the treatment of solid tumours. However, there is growing evidence that Src is also upregulated at very early stages of epithelial cancer development. We have investigated the role of Src in mouse skin, which is one of the most tractable models of epithelial homoeostasis and tumorigenesis. We found that Src protein expression and activity was regulated during the normal hair cycle and was increased specifically during the proliferative anagen phase and also in response to the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). AZD0530, a selective Src inhibitor, prevented the TPA-induced proliferation of basal keratinocytes both in vivo and in vitro. Moreover, treatment with AZD0530 reduced papilloma formation following the well-established 7,12-dimethylbenz(a)anthracene/TPA skin carcinogenesis protocol but did not inhibit the subsequent proliferation of the papillomas. Furthermore, AZD0530 did not alter the malignant conversion of papillomas to squamous cell carcinoma suggesting a role for Src in early tumour development in the skin carcinogenesis model, rather than at later stages of tumour progression. Src expression and activity were also seen in human actinic keratoses that are hyperproliferative pre-malignant skin lesions, indicating that Src may also play a role in the early stages of human skin tumour development. Thus, Src inhibitors such as AZD0530 may therefore have chemopreventative properties in patients with hyperproliferative epidermal disorders.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-57
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19060248-Adult, pubmed-meshheading:19060248-Aged, pubmed-meshheading:19060248-Animals, pubmed-meshheading:19060248-Anticarcinogenic Agents, pubmed-meshheading:19060248-Benzodioxoles, pubmed-meshheading:19060248-Carcinoma, Squamous Cell, pubmed-meshheading:19060248-Cell Line, Tumor, pubmed-meshheading:19060248-Cell Proliferation, pubmed-meshheading:19060248-Cell Transformation, Neoplastic, pubmed-meshheading:19060248-Disease Models, Animal, pubmed-meshheading:19060248-Female, pubmed-meshheading:19060248-Humans, pubmed-meshheading:19060248-Keratinocytes, pubmed-meshheading:19060248-Keratosis, pubmed-meshheading:19060248-Male, pubmed-meshheading:19060248-Mice, pubmed-meshheading:19060248-Middle Aged, pubmed-meshheading:19060248-Papilloma, pubmed-meshheading:19060248-Precancerous Conditions, pubmed-meshheading:19060248-Quinazolines, pubmed-meshheading:19060248-Skin Neoplasms, pubmed-meshheading:19060248-Tetradecanoylphorbol Acetate, pubmed-meshheading:19060248-src-Family Kinases
pubmed:year
2009
pubmed:articleTitle
A novel Src kinase inhibitor reduces tumour formation in a skin carcinogenesis model.
pubmed:affiliation
Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't