Effects of genistein on β-catenin signaling and subcellular distribution of actin-binding proteins in human umbilical CD105-positive stromal cells

Dar-Bin Shieh, Rui You Li, Jiuan Miaw Liao, Gin Den Chen, Ying Ming Liou

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-β-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.

Original languageEnglish
Pages (from-to)423-434
Number of pages12
JournalJournal of Cellular Physiology
Volume223
Issue number2
DOIs
Publication statusPublished - 2010 May 1

Fingerprint

Umbilicus
Microfilament Proteins
Catenins
Tropomyosin
Genistein
Stromal Cells
Cell proliferation
Profilins
Calmodulin-Binding Proteins
Actins
Signal transduction
Cell Proliferation
Signal Transduction
Stress Fibers
Messenger RNA
Cyclin D1
Protein Kinase Inhibitors
Actin Cytoskeleton
Fluorescence Microscopy
Immunoprecipitation

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

@article{4e2790268dd04c39a133d57cc3dbbc9c,
title = "Effects of genistein on β-catenin signaling and subcellular distribution of actin-binding proteins in human umbilical CD105-positive stromal cells",
abstract = "This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-β-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.",
author = "Dar-Bin Shieh and Li, {Rui You} and Liao, {Jiuan Miaw} and Chen, {Gin Den} and Liou, {Ying Ming}",
year = "2010",
month = "5",
day = "1",
doi = "10.1002/jcp.22051",
language = "English",
volume = "223",
pages = "423--434",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

Effects of genistein on β-catenin signaling and subcellular distribution of actin-binding proteins in human umbilical CD105-positive stromal cells. / Shieh, Dar-Bin; Li, Rui You; Liao, Jiuan Miaw; Chen, Gin Den; Liou, Ying Ming.

In: Journal of Cellular Physiology, Vol. 223, No. 2, 01.05.2010, p. 423-434.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of genistein on β-catenin signaling and subcellular distribution of actin-binding proteins in human umbilical CD105-positive stromal cells

AU - Shieh, Dar-Bin

AU - Li, Rui You

AU - Liao, Jiuan Miaw

AU - Chen, Gin Den

AU - Liou, Ying Ming

PY - 2010/5/1

Y1 - 2010/5/1

N2 - This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-β-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.

AB - This study was performed to define the roles of actin-binding proteins in the regulation of actin filament assembly associated with cellular signal transduction pathways in stromal cell proliferation. Genistein, a tyrosine protein kinase inhibitor, decreased the intracellular Ca2+ and attenuated cell proliferation and DNA synthesis through the β-catenin and cyclin D1 pathway in human umbilical CD105-positive cells. Immunoprecipitation studies using anti-β-actin antibody revealed that several actin-binding proteins implicated in cells include formin-2 (FMN-2), caldesmon (CaD), tropomyosin (Tm), and profilin. Protein levels of these proteins in whole cell lysates were not significantly changed by genistein. Three Tm isoforms, Tm-1, Tm-2, and Tm-4, were found to be present in cells. Genistein caused a reduction in levels of mRNAs coding for Tm-1 and Tm-4, but had no significant effect on Tm-2 mRNA levels. Immunofluorescence confocal scanning microscopy indicated that changes in the subcellular distribution of Tm and CaD, in which the diffuse cytosolic staining was shifted to show colocalization with actin stress fibers. In contrast, genistein-induced accumulation of FMN-2 and profilin in the peri-nuclear area. Silencing of FMN-2 by small interfering RNA resulted in increases of intracellular Ca2+ and rendered genistein resistance in decreasing intracellular Ca2+ in cells. These results provide the novel findings that genistein acts by modulating the cellular distribution of actin-binding proteins in association with alterations of cellular signal transduction pathways in human stromal cell proliferation.

UR - http://www.scopus.com/inward/record.url?scp=77950855926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950855926&partnerID=8YFLogxK

U2 - 10.1002/jcp.22051

DO - 10.1002/jcp.22051

M3 - Article

VL - 223

SP - 423

EP - 434

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -