PMID- 16363062
OWN - NLM
STAT- MEDLINE
DCOM- 20051228
LR  - 20161021
IS  - 1087-0024 (Print)
IS  - 1087-0024 (Linking)
VI  - 10
IP  - 2
DP  - 2005 Nov
TI  - Current view of the role of transforming growth factor beta 1 in skin 
      carcinogenesis.
PG  - 110-7
AB  - Previously, we have shown that transforming growth factor beta 1 (TGFbeta1) 
      overexpression in suprabasal epidermis suppresses skin carcinogenesis at early 
      stages, but promotes tumor invasion at later stages. To elucidate the role of 
      TGFbeta1 overexpression in naturally occurring human squamous cell carcinomas 
      (SCC), we screened TGFbeta1 expression patterns in human skin SCC samples and 
      found that TGFbeta1 was overexpressed with two distinct patterns: either 
      predominantly in suprabasal layers or throughout tumor epithelia including basal 
      proliferative cells. To determine the effect of TGFbeta1 overexpression in basal 
      keratinocytes, we generated transgenic mice expressing wild-type TGFbeta1 in 
      basal keratinocytes and hair follicles using the K5 promoter (K5.TGFbeta1(wt)). 
      Surprisingly, these mice developed a severe inflammatory skin disorder. 
      Inflammation was also observed in head and neck tissue when TGFbeta1 transgene 
      expression was inducibly expressed in head and neck epithelia in our 
      gene-switch-TGFbeta1 transgenic mice. Given the importance of inflammation in 
      cancer development, our data suggest that TGFbeta1-induced inflammation may 
      override its tumor-suppressive effect even at early stages of skin 
      carcinogenesis. This notion is further suggested by our recent study that Smad3 
      knockout mice were resistant to skin chemical carcinogenesis at least in part via 
      abrogation of endogenous TGFbeta1-induced inflammation.
FAU - Li, Allen Guanqun
AU  - Li AG
AD  - Department of Otolaryngology, Oregon Health & Science University, Portland, 
      Oregon, USA.
FAU - Lu, Shi-Long
AU  - Lu SL
FAU - Han, Gangwen
AU  - Han G
FAU - Kulesz-Martin, Molly
AU  - Kulesz-Martin M
FAU - Wang, Xiao-Jing
AU  - Wang XJ
LA  - eng
GR  - CA10549/CA/NCI NIH HHS/United States
GR  - CA79998/CA/NCI NIH HHS/United States
GR  - CA87849/CA/NCI NIH HHS/United States
GR  - DE15953/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - J Investig Dermatol Symp Proc
JT  - The journal of investigative dermatology. Symposium proceedings
JID - 9609059
RN  - 0 (Smad3 Protein)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Animals
MH  - Dermatitis/etiology
MH  - Humans
MH  - Psoriasis/etiology
MH  - Signal Transduction
MH  - Skin Neoplasms/*etiology
MH  - Smad3 Protein/physiology
MH  - Transforming Growth Factor beta/*physiology
MH  - Transforming Growth Factor beta1
RF  - 58
EDAT- 2005/12/21 09:00
MHDA- 2005/12/29 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2005/12/29 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - S0022-202X(15)52572-4 [pii]
AID - 10.1111/j.1087-0024.2005.200403.x [doi]
PST - ppublish
SO  - J Investig Dermatol Symp Proc. 2005 Nov;10(2):110-7. doi: 
      10.1111/j.1087-0024.2005.200403.x.