Tumor-suppressive function of mutated gelsolin in ras-transformed cells.
The flat revertant R1, isolated from human activated Ha-ras oncogene-transformed NIH3T3 fibroblasts (EJ-NIH3T3), expresses a variant form of the actin-regulatory protein gelsolin (p92-5.7). We have cloned cDNAs encoding p92-5.7 and identified as the cause of the expression of p92-5.7 a point mutation in codon 321, which results in an amino acid change from proline to histidine. In order to understand the role of p92-5.7 in reversion of ras-transformed cells, cDNAs encoding p92-5.7 or human authentic gelsolin as a control were transfected into EJ-NIH3T3 cells. All the transfectants that produced p92-5.7 and one of three transfectants that produced human authentic gelsolin either lost or reduced tumorigenicity in syngeneic mice. These results demonstrate that mutated gelsolin can suppress a ras tumor and suggest that authentic gelsolin, if expressed at increased levels, may have a similar suppressive potential. Our data propose an important role for gelsolin in cellular signal transduction pathways that involve the mammalian ras proto-oncogene.
Laboratory of Molecular Genetics, Hokkaido University School of Medicine, Sapporo, Japan.
L
L
Müllauer
H
H
Fujita
A
A
Ishizaki
N
N
Kuzumaki
D016475:3T3 Cells; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D018260:Gelsolin; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D066298:In Vitro Techniques; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
D002135:Calcium-Binding Proteins; D018260:Gelsolin; C000715470:MAS1 protein, human; D008840:Microfilament Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D016283:Proto-Oncogene Proteins p21(ras)