Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide

Alfredo F. Galvez, Liping Huang, Mark M J Magbanua, Kevin Dawson, Raymond L. Rodriguez

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5′ region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.

Original languageEnglish (US)
Pages (from-to)623-636
Number of pages14
JournalNutrition and Cancer
Volume63
Issue number4
DOIs
StatePublished - May 2011

Fingerprint

Thrombospondins
Chromatin
Prostate
Acetylation
Epithelial Cells
Histone Acetyltransferases
Peptides
CpG Islands
Histones
Up-Regulation
Genes
Chromatin Immunoprecipitation
Gene Expression Profiling
DNA Sequence Analysis
Cultured Cells
Gene Expression
Polymerase Chain Reaction
Acids
DNA
Enzymes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Oncology
  • Cancer Research

Cite this

Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide. / Galvez, Alfredo F.; Huang, Liping; Magbanua, Mark M J; Dawson, Kevin; Rodriguez, Raymond L.

In: Nutrition and Cancer, Vol. 63, No. 4, 05.2011, p. 623-636.

Research output: Contribution to journalArticle

Galvez, Alfredo F. ; Huang, Liping ; Magbanua, Mark M J ; Dawson, Kevin ; Rodriguez, Raymond L. / Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide. In: Nutrition and Cancer. 2011 ; Vol. 63, No. 4. pp. 623-636.
@article{e9a2c76f809f44b09365161da518af21,
title = "Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide",
abstract = "The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5′ region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.",
author = "Galvez, {Alfredo F.} and Liping Huang and Magbanua, {Mark M J} and Kevin Dawson and Rodriguez, {Raymond L.}",
year = "2011",
month = "5",
doi = "10.1080/01635581.2011.539312",
language = "English (US)",
volume = "63",
pages = "623--636",
journal = "Nutrition and Cancer",
issn = "0163-5581",
publisher = "Routledge",
number = "4",

}

TY - JOUR

T1 - Differential expression of thrombospondin (THBS1) in tumorigenic and nontumorigenic prostate epithelial cells in response to a chromatin-binding soy peptide

AU - Galvez, Alfredo F.

AU - Huang, Liping

AU - Magbanua, Mark M J

AU - Dawson, Kevin

AU - Rodriguez, Raymond L.

PY - 2011/5

Y1 - 2011/5

N2 - The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5′ region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.

AB - The chemopreventive properties of the chromatin-binding soy peptide, lunasin, are well documented, but its mechanism of action is unclear. To elucidate the mechanism by which lunasin reduces tumor foci formation in cultured mammalian cells, nontumorigenic (RWPE-1) and tumorigenic (RWPE-2) human prostate epithelial cells were treated with lunasin followed by gene expression profiling and characterization of the chromatin acetylation status for certain chemopreventive genes. The genes HIF1A, PRKAR1A, TOB1, and THBS1 were upregulated by lunasin in RWPE-1 but not in RWPE-2 cells. Using histone acetyltransferase (HAT) assays with acid-extracted histones as templates, we showed that lunasin specifically inhibited H4K8 acetylation while enhanced H4K16 acetylation catalyzed by HAT enzymes p300, PCAF, and HAT1A. These results suggest a novel mechanism for lunasin-dependent upregulation of gene expression. Chromatin immunoprecipitation (ChIP) revealed hypoacetylation of H4K16 in RWPE-2 cells, specifically at the 5' end of THBS1 containing a CpG island. Moreover, bisulfite PCR (BSP) and subsequent DNA sequencing indicated that this CpG island was hypomethylated in RWPE-1 but hypermethylated in RWPE-2 cells. Histone hypoacetylation and DNA hypermethylation in the 5′ region of THBS1 may explain the inability of lunasin to upregulate this gene in RWPE-2 cells.

UR - http://www.scopus.com/inward/record.url?scp=79957584040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957584040&partnerID=8YFLogxK

U2 - 10.1080/01635581.2011.539312

DO - 10.1080/01635581.2011.539312

M3 - Article

C2 - 21526452

AN - SCOPUS:79957584040

VL - 63

SP - 623

EP - 636

JO - Nutrition and Cancer

JF - Nutrition and Cancer

SN - 0163-5581

IS - 4

ER -