Document Detail

TGF alpha is dispensable for skin tumorigenesis in Tg.AC mice.
MedLine Citation:
PMID:  9715516     Owner:  NLM     Status:  MEDLINE    
Alterations in growth factor signaling pathways frequently accompany the development and maintenance of epithelial neoplasia. Transforming growth factor alpha (TGF alpha) and its epidermal growth factor receptor have been thought to play an especially important role in epithelial neoplasia. In this study, mice were derived genetically deficient (null) in functional TGF alpha expression and carrying the Tg.AC/v-Ha-ras transgene. The goals were to determine if (a) papillomagenesis was dependent on TGF alpha and (b) progression to malignancy was dependent on TGF alpha expression. Groups of male and female mice heterozygous or homozygous for the TGF alpha null allele and hemizygous for the Tg.AC transgene were treated twice weekly for 10 or 15 wk with doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) known to produce papillomas in Tg.AC mice. Papillomas were readily induced in both male and female TGF alpha null mice. Malignant progression of papillomas was observed in all TGF alpha null treatment groups. Additionally, we examined the response of TGF alpha null mice to full thickness dorsal wounds, a stimulus known to promote papillomagenesis in Tg.AC mice. As in the TPA study, papillomas were induced in both male and female TGF alpha null mice. These studies indicate that TGF alpha is not required for the induction and maintenance of papillomas nor is it essential for the malignant conversion of papillomas in Tg.AC mice.
M C Humble; C J Szczesniak; N C Luetteke; J W Spalding; R E Cannon; L A Hansen; D C Lee; R W Tennant
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicologic pathology     Volume:  26     ISSN:  0192-6233     ISO Abbreviation:  Toxicol Pathol     Publication Date:    1998 Jul-Aug
Date Detail:
Created Date:  1998-11-16     Completed Date:  1998-11-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7905907     Medline TA:  Toxicol Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  562-9     Citation Subset:  IM    
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514, USA.
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MeSH Terms
Carcinogens / metabolism
Carcinoma / chemically induced,  pathology*
Carcinoma, Squamous Cell / chemically induced,  pathology*
Mice, Transgenic
Papilloma / chemically induced,  pathology*
Receptor, Epidermal Growth Factor / biosynthesis,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms / chemically induced,  pathology*
Transforming Growth Factor alpha / deficiency,  genetics,  physiology*
Wound Healing
Grant Support
Reg. No./Substance:
0/Carcinogens; 0/Transforming Growth Factor alpha; EC, Epidermal Growth Factor

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