Linked Life Data

11280804

Source:http://linkedlifedata.com/resource/pubmed/id/11280804

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-3-30
pubmed:abstractText
The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in tumorigenesis is complex. On the one hand, GM-CSF can promote tumor cell growth, survival, and even metastasis. On the other hand, it can stimulate tumor cell rejection. In skin, it is early expressed after topic application of tumor-promoting agents and therefore may be responsible for changes that correlate with skin tumor promotion (e.g., epidermal hyperproliferation and inflammation). To analyze GM-CSF function in skin tumorigenesis, we generated transgenic mice epidermally overexpressing either GM-CSF or a GM-CSF antagonist. Both types of transgenic mice exhibited significantly increased numbers of benign tumors in a two-step skin carcinogenesis experiment using 7',12'-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-CSF displayed a significantly elevated carcinoma burden following a single-step carcinogenesis protocol consisting of tumor initiation only. Therefore, endogenous promotion is responsible for elevated tumor development in GM-CSF-overexpressing mice. In antagonist transgenic animals, an increased tumorigenicity of modified B16 tumor cells after cutaneous transplantation as compared with nontransgenic or GM-CSF transgenic mice was observed. Thus, the antitumor activity leading to the repression of tumor cell growth in control mice is GM-CSF dependent and is compromised in mice expressing the antagonist. We suggest that both, up-regulation and down-regulation of GM-CSF activity in skin, increase the incidence and growth of tumors via two independent mechanisms: endogenous tumor promotion in the case of increased GM-CSF activity and compromised tumor cell rejection in the case of decreased GM-CSF activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2311-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11280804-9,10-Dimethyl-1,2-benzanthracene, pubmed-meshheading:11280804-Animals, pubmed-meshheading:11280804-Carcinogens, pubmed-meshheading:11280804-Down-Regulation, pubmed-meshheading:11280804-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:11280804-Keratin-10, pubmed-meshheading:11280804-Keratins, pubmed-meshheading:11280804-Melanoma, Experimental, pubmed-meshheading:11280804-Mice, pubmed-meshheading:11280804-Mice, Transgenic, pubmed-meshheading:11280804-Neoplasm Transplantation, pubmed-meshheading:11280804-Phenotype, pubmed-meshheading:11280804-Skin, pubmed-meshheading:11280804-Skin Neoplasms, pubmed-meshheading:11280804-Skin Physiological Phenomena, pubmed-meshheading:11280804-Tetradecanoylphorbol Acetate, pubmed-meshheading:11280804-Transgenes, pubmed-meshheading:11280804-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Up- and down-regulation of granulocyte/macrophage-colony stimulating factor activity in murine skin increase susceptibility to skin carcinogenesis by independent mechanisms.
pubmed:affiliation
Medical Department, Johannes Gutenberg-University, Mainz, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't