Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression

Ho Jeong Kwon, Minoru Yoshida, Rie Nagaoka, Takashi Obinata, Teruhiko Beppu, Sueharu Horinouchi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cell lines and to revert their cell morphology to be flat. In the radicicol-treated flat cells, actin stress fiber bundles were reorganized. Since this effect of radicicol on these cell lines was inhibited by cycloheximide, de novo protein synthesis is required for the morphological reversion. Screening of cellular proteins enhanced in response to radicicol by two-dimensional gel electrophoresis suggested that the amount of gelsolin, an actin regulatory protein, was distinctly increased upon radicicol treatment. Western blot and Northern blot analyses showed that radicicol enhanced transcription of the gelsolin gene in human carcinoma cell lines, as a result of which the amount of gelsolin was increased several folds. Injection with an anti-gelsolin antibody into cells and successive treatment with radicicol resulted in approximately 80% reduction of the number of flat cells with stress fibers in comparison with controls treated with an irrelevant antibody. These results show that elevated expression of gelsolin is associated, at least in part, suppression of transformation and the restoration actin stress fibers in human carcinoma cells by radicicol.

Original languageEnglish
Pages (from-to)2625-2631
Number of pages7
JournalOncogene
Volume15
Issue number21
DOIs
Publication statusPublished - 1997 Jan 1

Fingerprint

Gelsolin
Stress Fibers
Actins
src-Family Kinases
Carcinoma
Cell Line
monorden
Transformed Cell Line
Proteins
G2 Phase
Electrophoresis, Gel, Two-Dimensional
G1 Phase
Cycloheximide
Cell Cycle Checkpoints
Oncogenes
Northern Blotting
Anti-Idiotypic Antibodies
Fibroblasts
Cell Count
Western Blotting

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Kwon, Ho Jeong ; Yoshida, Minoru ; Nagaoka, Rie ; Obinata, Takashi ; Beppu, Teruhiko ; Horinouchi, Sueharu. / Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression. In: Oncogene. 1997 ; Vol. 15, No. 21. pp. 2625-2631.
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Kwon, HJ, Yoshida, M, Nagaoka, R, Obinata, T, Beppu, T & Horinouchi, S 1997, 'Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression', Oncogene, vol. 15, no. 21, pp. 2625-2631. https://doi.org/10.1038/sj.onc.1201443

Suppression of morphological transformation by radicicol is accompanied by enhanced gelsolin expression. / Kwon, Ho Jeong; Yoshida, Minoru; Nagaoka, Rie; Obinata, Takashi; Beppu, Teruhiko; Horinouchi, Sueharu.

In: Oncogene, Vol. 15, No. 21, 01.01.1997, p. 2625-2631.

Research output: Contribution to journalArticle

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AU - Kwon, Ho Jeong

AU - Yoshida, Minoru

AU - Nagaoka, Rie

AU - Obinata, Takashi

AU - Beppu, Teruhiko

AU - Horinouchi, Sueharu

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AB - Radicicol, an inhibitor of Src-family protein-tyrosine kinases, causes morphological reversion of v-src- and v-Ha-ras-transformed fibroblasts and arrest of the cell cycle at both the G1 and the G2 phases. Radicicol was found to inhibit the growth of several other oncogene-transformed cell lines and human carcinoma cell lines and to revert their cell morphology to be flat. In the radicicol-treated flat cells, actin stress fiber bundles were reorganized. Since this effect of radicicol on these cell lines was inhibited by cycloheximide, de novo protein synthesis is required for the morphological reversion. Screening of cellular proteins enhanced in response to radicicol by two-dimensional gel electrophoresis suggested that the amount of gelsolin, an actin regulatory protein, was distinctly increased upon radicicol treatment. Western blot and Northern blot analyses showed that radicicol enhanced transcription of the gelsolin gene in human carcinoma cell lines, as a result of which the amount of gelsolin was increased several folds. Injection with an anti-gelsolin antibody into cells and successive treatment with radicicol resulted in approximately 80% reduction of the number of flat cells with stress fibers in comparison with controls treated with an irrelevant antibody. These results show that elevated expression of gelsolin is associated, at least in part, suppression of transformation and the restoration actin stress fibers in human carcinoma cells by radicicol.

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