PMID- 9349822
OWN - NLM
STAT- MEDLINE
DCOM- 19971113
LR  - 20220228
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 389
IP  - 6653
DP  - 1997 Oct 23
TI  - Activation of the transcription factor Gli1 and the Sonic hedgehog signalling 
      pathway in skin tumours.
PG  - 876-81
AB  - Sporadic basal cell carcinoma (BCC) is the most common type of malignant cancer 
      in fair-skinned adults. Familial BCCs and a fraction of sporadic BCCs have lost 
      the function of Patched (Ptc), a Sonic hedgehog (Shh) receptor that acts 
      negatively on this signalling pathway. Overexpression of Shh can induce BCCs in 
      mice. Here we show that ectopic expression of the zinc-finger transcription 
      factor Gli1 in the embryonic frog epidermis results in the development of tumours 
      that express endogenous Gli1. We also show that Shh and the Gli genes are 
      normally expressed in hair follicles, and that human sporadic BCCs consistently 
      express Gli1 but not Shh or Gli3. Because Gli1, but not Gli3, acts as a target 
      and mediator of Shh signalling, our results suggest that expression of Gli1 in 
      basal cells induces BCC formation. Moreover, loss of Ptc or overexpression of Shh 
      cannot be the sole causes of Gli1 induction and sporadic BCC formation, as they 
      do not occur consistently. Thus any mutations leading to the expression of Gli1 
      in basal cells are predicted to induce BCC formation.
FAU - Dahmane, N
AU  - Dahmane N
AD  - The Skirball Institute, Department of Cell Biology, New York University Medical 
      Center, New York 10016, USA.
FAU - Lee, J
AU  - Lee J
FAU - Robins, P
AU  - Robins P
FAU - Heller, P
AU  - Heller P
FAU - Ruiz i Altaba, A
AU  - Ruiz i Altaba A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Proteins)
RN  - 0 (Ptch1 protein, mouse)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (SHH protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
SB  - IM
EIN - Nature 1997 Dec 4;390(6659):536
MH  - Animals
MH  - Carcinoma, Basal Cell/embryology/genetics/*metabolism
MH  - Cell Transformation, Neoplastic
MH  - Embryo, Nonmammalian
MH  - Gene Expression
MH  - Hair Follicle/metabolism
MH  - Hedgehog Proteins
MH  - Humans
MH  - Membrane Proteins/genetics/metabolism
MH  - Mutation
MH  - Oncogene Proteins/genetics/*metabolism
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Proteins/genetics/*metabolism
MH  - Receptors, Cell Surface
MH  - *Signal Transduction
MH  - Skin Neoplasms/embryology/genetics/*metabolism
MH  - *Trans-Activators
MH  - Transcription Factors/genetics/*metabolism
MH  - Xenopus laevis
MH  - Zinc Finger Protein GLI1
MH  - *Zinc Fingers
EDAT- 1998/02/12 04:52
MHDA- 2001/03/23 10:01
CRDT- 1998/02/12 04:52
PHST- 1998/02/12 04:52 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1998/02/12 04:52 [entrez]
AID - 10.1038/39918 [doi]
PST - ppublish
SO  - Nature. 1997 Oct 23;389(6653):876-81. doi: 10.1038/39918.