Expression of two types of neurofibromatosis type 1 gene transcripts in gastric cancers and comparison of GAP activities.
To understand the molecular mechanism of gastric tumorigenesis, the status of neurofibromatosis type 1 (NF1) gene was analyzed in human gastric cancer cell lines. Although the sequencing of the GTPase activating protein (GAP)-related region of NF1 (NF1-GRD) revealed no apparent mutation, the NF1-GRD transcript (type I) and that containing an additional 63 bp insert in the center of NF1-GRD (type II) were equally expressed in most gastric cancer cells. By contrast, type II was predominantly expressed in normal stomach mucosa. When these two types of NF1-GRD were bacterially expressed and their GAP activities were tested, both types of NF1-GRD similarly stimulated ras GTPase activity. However, arachidonic acid inhibited GAP activities of two types of NF1-GRD to different extents. These results suggest that the increased expression of type I NF1 protein may modulate ras-related signal transduction and it may be related to the control of the gastric cellular proliferation.
Uchida
T
T
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Matozaki
T
T
Suzuki
T
T
Matsuda
K
K
Wada
K
K
Nakano
O
O
Konda
Y
Y
Nishisaki
H
H
Nagao
M
M
Sakamoto
C
C
D016718:Arachidonic Acid / Q000494:pharmacology; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D020690:GTPase-Activating Proteins; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression; D016514:Genes, Neurofibromatosis 1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic; D020703:ras GTPase-Activating Proteins
D020690:GTPase-Activating Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D020703:ras GTPase-Activating Proteins; D016718:Arachidonic Acid; D004247:DNA