Linked Life Data

15208685

Source:http://linkedlifedata.com/resource/pubmed/id/15208685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
35
pubmed:dateCreated
2004-8-5
pubmed:abstractText
The homeostatic integrity of skin epidermis is maintained by a balance between keratinocyte proliferation, on one hand, and terminal differentiation combined with outward migration and shedding, on the other. Perturbation of this balance in favor of proliferation can result in hyperplasia and, potentially, tumorigenesis. We have previously described a reversible transgenic mouse model of epidermal neoplasia in which expression of an acutely regulatable form of Myc, MycERTAM, is targeted to epidermis via the involucrin promoter. In this model, sustained activation of MycERTAM induces a complex neoplastic lesion involving marked hyperplasia of less-differentiated suprabasal cells, angiogenesis and overt papillomatosis. Subsequent deactivation of MycERTAM triggers complete papilloma regression. Here, we provide evidence that Myc-induced papillomas are self-limiting because of the eventual differentiation of MycERTAM-expressing keratinocytes. Thus, keratinocyte differentiation eventually prevails over Myc-induced proliferation. We also show that regression of Myc-induced papillomas following MycERTAM deactivation occurs through a combination of growth arrest and irreversible differentiation. Finally, we demonstrate that transient deactivation of Myc is sufficient to expel keratinocytes irreversibly from the proliferative compartment and render them refractory to the mitogenic influence of subsequent Myc reactivation. Such observations illustrate the potential utility of even short-term inhibition of oncogenic lesions in the treatment of cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5923-30
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Defining the temporal requirements for Myc in the progression and maintenance of skin neoplasia.
pubmed:affiliation
Cancer Research Institute, University of California at San Francisco, 2340 Sutter St, San Francisco, CA 94143-0875, USA.
pubmed:publicationType
Journal Article