PMID- 9715516
OWN - NLM
STAT- MEDLINE
DCOM- 19981116
LR  - 20181201
IS  - 0192-6233 (Print)
IS  - 0192-6233 (Linking)
VI  - 26
IP  - 4
DP  - 1998 Jul-Aug
TI  - TGF alpha is dispensable for skin tumorigenesis in Tg.AC mice.
PG  - 562-9
AB  - 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.
FAU - Humble, M C
AU  - Humble MC
AD  - Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514, USA.
FAU - Szczesniak, C J
AU  - Szczesniak CJ
FAU - Luetteke, N C
AU  - Luetteke NC
FAU - Spalding, J W
AU  - Spalding JW
FAU - Cannon, R E
AU  - Cannon RE
FAU - Hansen, L A
AU  - Hansen LA
FAU - Lee, D C
AU  - Lee DC
FAU - Tennant, R W
AU  - Tennant RW
LA  - eng
GR  - CA43793/CA/NCI NIH HHS/United States
GR  - T32 ES07126/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Toxicol Pathol
JT  - Toxicologic pathology
JID - 7905907
RN  - 0 (Carcinogens)
RN  - 0 (Transforming Growth Factor alpha)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Animals
MH  - Carcinogens/metabolism
MH  - Carcinoma/chemically induced/*pathology
MH  - Carcinoma, Squamous Cell/chemically induced/*pathology
MH  - ErbB Receptors/biosynthesis/genetics
MH  - Female
MH  - Genotype
MH  - Mice
MH  - Mice, Transgenic
MH  - Papilloma/chemically induced/*pathology
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin Neoplasms/chemically induced/*pathology
MH  - Transforming Growth Factor alpha/deficiency/genetics/*physiology
MH  - Wound Healing
EDAT- 1998/08/26 00:00
MHDA- 1998/08/26 00:01
CRDT- 1998/08/26 00:00
PHST- 1998/08/26 00:00 [pubmed]
PHST- 1998/08/26 00:01 [medline]
PHST- 1998/08/26 00:00 [entrez]
AID - 10.1177/019262339802600413 [doi]
PST - ppublish
SO  - Toxicol Pathol. 1998 Jul-Aug;26(4):562-9. doi: 10.1177/019262339802600413.