Ral promotes anchorage-independent growth of a human fibrosarcoma, HT1080.
Ral has been shown to act downstream of Ras oncoprotein. However, the role of Ral in Ras-induced cellular transformation has not been fully understood. To test the involvement of Ral in Ras-induced anchorage-independent growth, we ectopically expressed Ral mutants in HT1080 cells, whose ability to grow in the absence of anchorage depends on the oncogenic mutation of N-ras. Expression of an activated mutant of Ral resulted in enhanced growth of HT1080 cells in soft agar, whereas a dominant-negative mutant of Ral inhibited their anchorage-independent growth. Moreover, the activated Ral mutant decreased the amount of p27(Kip1) in the absence of adhesion, while the dominant-negative mutant increased it. These results suggest that Ral is involved in the Ras-dependent anchorage-independent growth of HT1080 cells by regulating p27(Kip1).
Yamazaki
Y
Y
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
Kaziro
Y
Y
Koide
H
H
D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017931:DNA Primers / Q000235:genetics; D005354:Fibrosarcoma / Q000235:genetics / Q000473:pathology; D011905:Genes, ras; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000502:physiology; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D020725:ral GTP-Binding Proteins