PMID- 19142899
OWN - NLM
STAT- MEDLINE
DCOM- 20090818
LR  - 20220224
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Linking)
VI  - 48
IP  - 8
DP  - 2009 Aug
TI  - Regulation of the hedgehog signaling by the mitogen-activated protein kinase 
      cascade in gastric cancer.
PG  - 703-12
LID - 10.1002/mc.20516 [doi]
AB  - The hedgehog and mitogen-activated protein kinase (MAPK) signaling pathways 
      regulate growth in many tumors, suggesting cooperation between these two pathways 
      in the regulation of cell proliferation. However, interactions between these 
      pathways have not been extensively studied. We assessed cross-talk between 
      hedgehog and MAPK signaling in the regulation of cell proliferation in gastric 
      cancer. We showed that PTCH expression was significantly correlated with 
      extracellular signal-regulated kinase (ERK) 1/2 phosphorylation (P = 0.016) as 
      well as SHH expression (P = 0.034) in the 35 gastric cancers assessed by 
      immunohistochemistry. Indeed, MAPK signaling increased the GLI transcriptional 
      activity and induced the expression of hedgehog target genes in gastric cancer 
      cells. The inductive effect of activated KRAS and mitogen-activated 
      protein/extracellular signal-regulated kinase kinase (MEK) 1 was blocked by the 
      suppressor of fused (SUFU), indicating that MAPK signaling regulates GLI activity 
      via a SUFU-independent process. Moreover, the deletion of the NH2-terminal domain 
      of GLI1 gene resulted in reduced response to MEK1 stimulation. Our results 
      suggest that the KRAS-MEK-ERK cascade has a positive regulatory role in GLI 
      transcriptional activity in gastric cancer.
FAU - Seto, Motoko
AU  - Seto M
AD  - Department of Gastroenterology, Graduate School of Medicine, The University of 
      Tokyo, Bunkyo-ku, Tokyo, Japan.
FAU - Ohta, Miki
AU  - Ohta M
FAU - Asaoka, Yoshinari
AU  - Asaoka Y
FAU - Ikenoue, Tsuneo
AU  - Ikenoue T
FAU - Tada, Motohisa
AU  - Tada M
FAU - Miyabayashi, Koji
AU  - Miyabayashi K
FAU - Mohri, Dai
AU  - Mohri D
FAU - Tanaka, Yasuo
AU  - Tanaka Y
FAU - Ijichi, Hideaki
AU  - Ijichi H
FAU - Tateishi, Keisuke
AU  - Tateishi K
FAU - Kanai, Fumihiko
AU  - Kanai F
FAU - Kawabe, Takao
AU  - Kawabe T
FAU - Omata, Masao
AU  - Omata M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - 0 (GLI1 protein, human)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched Receptors)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Repressor Proteins)
RN  - 0 (SHH protein, human)
RN  - 0 (SUFU protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Adenocarcinoma, Mucinous/genetics/metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Blotting, Western
MH  - Carcinoma, Papillary/genetics/metabolism/pathology
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Amplification
MH  - Hedgehog Proteins/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Patched Receptors
MH  - Patched-1 Receptor
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Cell Surface/genetics/*metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stomach Neoplasms/genetics/*metabolism/pathology
MH  - Transcription Factors/*genetics/metabolism
MH  - Zinc Finger Protein GLI1
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
MH  - ras Proteins/metabolism
EDAT- 2009/01/15 09:00
MHDA- 2009/08/19 09:00
CRDT- 2009/01/15 09:00
PHST- 2009/01/15 09:00 [entrez]
PHST- 2009/01/15 09:00 [pubmed]
PHST- 2009/08/19 09:00 [medline]
AID - 10.1002/mc.20516 [doi]
PST - ppublish
SO  - Mol Carcinog. 2009 Aug;48(8):703-12. doi: 10.1002/mc.20516.