PMID- 9422511
OWN - NLM
STAT- MEDLINE
DCOM- 19980115
LR  - 20220309
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 391
IP  - 6662
DP  - 1998 Jan 1
TI  - Activating Smoothened mutations in sporadic basal-cell carcinoma.
PG  - 90-2
AB  - Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their 
      genesis came from identification of mutations in the PATCHED gene (PTCH) in 
      patients with the basal-cell nevus syndrome, a hereditary disease characterized 
      by multiple BCCs and by developmental abnormalities. The binding of Sonic 
      hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by 
      PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this 
      model, the inhibition of SMO signalling is relieved following mutational 
      inactivation of PTCH in basal-cell nevus syndrome. We report here the 
      identification of activating somatic missense mutations in the SMO gene itself in 
      sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate 
      with adenovirus E1A to transform rat embryonic fibroblast cells in culture. 
      Furthermore, skin abnormalities similar to BCCs developed in transgenic murine 
      skin overexpressing mutant SMO. These findings support the role of SMO as a 
      signalling component of the SHH-receptor complex and provide direct evidence that 
      mutated SMO can function as an oncogene in BCCs.
FAU - Xie, J
AU  - Xie J
AD  - Department of Dermatology, San Francisco General Hospital, University of 
      California, 94110, USA.
FAU - Murone, M
AU  - Murone M
FAU - Luoh, S M
AU  - Luoh SM
FAU - Ryan, A
AU  - Ryan A
FAU - Gu, Q
AU  - Gu Q
FAU - Zhang, C
AU  - Zhang C
FAU - Bonifas, J M
AU  - Bonifas JM
FAU - Lam, C W
AU  - Lam CW
FAU - Hynes, M
AU  - Hynes M
FAU - Goddard, A
AU  - Goddard A
FAU - Rosenthal, A
AU  - Rosenthal A
FAU - Epstein, E H Jr
AU  - Epstein EH Jr
FAU - de Sauvage, F J
AU  - de Sauvage FJ
LA  - eng
SI  - GENBANK/AF114819
SI  - GENBANK/AF114820
SI  - GENBANK/AF114821
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Adenovirus E1A Proteins)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Proteins)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Ptch1 protein, rat)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (SHH protein, human)
RN  - 0 (SMO protein, human)
RN  - 0 (Smo protein, mouse)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Adenovirus E1A Proteins/genetics/physiology
MH  - Animals
MH  - Carcinoma, Basal Cell/*genetics
MH  - Cell Line
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 7
MH  - Hedgehog Proteins
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Membrane Proteins/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - *Mutation
MH  - Oncogenes
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Polymerase Chain Reaction
MH  - Protein Conformation
MH  - Proteins/metabolism
MH  - Rats
MH  - Receptors, Cell Surface/chemistry/*genetics/physiology
MH  - *Receptors, G-Protein-Coupled
MH  - Signal Transduction
MH  - Skin Neoplasms/*genetics
MH  - Smoothened Receptor
MH  - *Trans-Activators
MH  - Transfection
EDAT- 1998/01/09 05:16
MHDA- 2001/03/23 10:01
CRDT- 1998/01/09 05:16
PHST- 1998/01/09 05:16 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1998/01/09 05:16 [entrez]
AID - 10.1038/34201 [doi]
PST - ppublish
SO  - Nature. 1998 Jan 1;391(6662):90-2. doi: 10.1038/34201.