Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-6-22
pubmed:abstractText
To assess the requirements for papilloma formation in transgenic mice that overexpress transforming growth factor-alpha (TGF-alpha) in the epidermis (HK1.TGF alpha), we tested the sensitivity of HK1.TGF alpha mice to tumor promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA) and analyzed the resultant papillomas for synergic c-Ha-ras activation and overexpression. We observed that HK1.TGF alpha mice were highly sensitive to TPA promotion, exhibiting multiple papillomas as early as the third week of treatment. After 60 wk of promotion, malignant conversion was not observed and tumors regressed upon removal of the TPA promotion stimulus. Most of the TPA-induced papillomas did not have detectable c-Ha-ras mutations at codons 12, 13, or 61, but three papillomas arising after long-term TPA promotion (5-7 mo) exhibited c-Ha-ras activation at codon 61 (A-->T and A-->G). Conversely, spontaneous papillomas arising without TPA promotion, including persisting autonomous papillomas, were all negative for activating c-Ha-ras mutations. Both spontaneous and TPA-induced HK1.TGF alpha papillomas expressed c-Ha-ras message levels similar to those in normal, nontransgenic epidermis or HK1.TGF alpha hyperplastic epidermis. These data demonstrate that TGF-alpha overexpression can be an initiating event for TPA promotion, that papillomatogenesis in HK1.TGF alpha mice proceeds frequently via a pathway independent of Ha-ras activation or overexpression, and, thus, that other events are required for autonomous growth and malignant conversion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0899-1987
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Epidermal expression of transforming growth factor-alpha in transgenic mice: induction of spontaneous and 12-O-tetradecanoylphorbol-13-acetate-induced papillomas via a mechanism independent of Ha-ras activation or overexpression.
pubmed:affiliation
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't