PMID- 17230190
OWN - NLM
STAT- MEDLINE
DCOM- 20070307
LR  - 20201113
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Linking)
VI  - 445
IP  - 7129
DP  - 2007 Feb 15
TI  - Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the 
      Patched gene in FVB mice.
PG  - 761-5
AB  - Mice of the C57BL/6 strain are resistant to the development of skin squamous 
      carcinomas (SCCs) induced by an activated Ras oncogene, whereas FVB/N mice are 
      highly susceptible. The genetic basis of this difference in phenotype is unknown. 
      Here we show that susceptibility to SCC is under the control of a 
      carboxy-terminal polymorphism in the mouse Ptch gene. F1 hybrids between C57BL/6 
      and FVB/N strains ((B6FVB)F1) are resistant to Ras-induced SCCs, but resistance 
      can be overcome either by elimination of the C57BL/6 Ptch allele (Ptch(B6)) or by 
      overexpression of the FVB/N Ptch allele (Ptch(FVB)) in the epidermis of 
      K5Hras-transgenic (B6FVB)F1 hybrid mice. The human Patched (PTCH) gene is a 
      classical tumour suppressor gene for basal cell carcinomas and medulloblastomas, 
      the loss of which causes increased signalling through the Sonic Hedgehog (SHH) 
      pathway. SCCs that develop in PtchB6+/- mice do not lose the wild-type Ptch gene 
      or show evidence of increased SHH signalling. Although Ptch(FVB) overexpression 
      can promote SCC formation, continued expression is not required for tumour 
      maintenance, suggesting a role at an early stage of tumour cell lineage 
      commitment. The Ptch polymorphism affects Hras-induced apoptosis, and binding to 
      Tid1, the mouse homologue of the Drosophila l(2)tid tumour suppressor gene. We 
      propose that Ptch occupies a critical niche in determining basal or squamous cell 
      lineage, and that both tumour types can arise from the same target cell depending 
      on carcinogen exposure and host genetic background.
FAU - Wakabayashi, Yuichi
AU  - Wakabayashi Y
AD  - Cancer Research Institute, University of California at San Francisco, 2340 Sutter 
      Street, San Francisco, California 94143, USA.
FAU - Mao, Jian-Hua
AU  - Mao JH
FAU - Brown, Ken
AU  - Brown K
FAU - Girardi, Michael
AU  - Girardi M
FAU - Balmain, Allan
AU  - Balmain A
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20070117
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Dnaja3 protein, mouse)
RN  - 0 (Gli2 protein, mouse)
RN  - 0 (HSP40 Heat-Shock Proteins)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Zinc Finger Protein Gli2)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis
MH  - Carcinoma, Squamous Cell/*genetics/*pathology
MH  - Cell Line
MH  - Cell Transformation, Neoplastic
MH  - Crosses, Genetic
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - *Genes, ras
MH  - HSP40 Heat-Shock Proteins/metabolism
MH  - Humans
MH  - Kruppel-Like Transcription Factors/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Polymorphism, Genetic/*genetics
MH  - Receptors, Cell Surface/*genetics/metabolism
MH  - Zinc Finger Protein Gli2
MH  - ras Proteins/genetics/*metabolism
EDAT- 2007/01/19 09:00
MHDA- 2007/03/08 09:00
CRDT- 2007/01/19 09:00
PHST- 2006/08/25 00:00 [received]
PHST- 2006/11/27 00:00 [accepted]
PHST- 2007/01/19 09:00 [pubmed]
PHST- 2007/03/08 09:00 [medline]
PHST- 2007/01/19 09:00 [entrez]
AID - nature05489 [pii]
AID - 10.1038/nature05489 [doi]
PST - ppublish
SO  - Nature. 2007 Feb 15;445(7129):761-5. doi: 10.1038/nature05489. Epub 2007 Jan 17.