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Tumor-suppressive function of mutated gelsolin in ras-transformed cells
L Müllauer1, H Fujita, A Ishizaki
1Laboratory of Molecular Genetics, Hokkaido University School of Medicine, Sapporo, Japan.
Oncogene
|September 1, 1993
Summary
Mutated gelsolin (p92-5.7) suppressed ras-transformed cell tumors. Authentic gelsolin may also suppress tumors, highlighting gelsolin's role in ras signaling pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- NIH3T3 fibroblasts transformed with the Ha-ras oncogene (EJ-NIH3T3) can exhibit a reverted phenotype.
- The flat revertant R1 expresses a variant actin-regulatory protein, gelsolin (p92-5.7).
Purpose of the Study:
- To investigate the role of mutated gelsolin (p92-5.7) in suppressing the tumorigenicity of ras-transformed cells.
- To determine if authentic human gelsolin also possesses tumor-suppressive properties.
Main Methods:
- Cloning of cDNAs encoding p92-5.7 and authentic human gelsolin.
- Transfection of EJ-NIH3T3 cells with these cDNAs.
- Assessment of tumorigenicity in syngeneic mice.
Main Results:
- A point mutation (proline to histidine at codon 321) was identified as the cause of p92-5.7 expression.
- Transfectants expressing p92-5.7 showed reduced or lost tumorigenicity.
- One of three transfectants expressing authentic human gelsolin also exhibited reduced tumorigenicity.
Conclusions:
- Mutated gelsolin (p92-5.7) can suppress ras-induced tumors.
- Authentic gelsolin may possess similar tumor-suppressive potential when expressed at higher levels.
- Gelsolin plays a significant role in cellular signal transduction pathways involving the mammalian ras proto-oncogene.