Critical role of extracellular signal-regulated kinase (ERK) phosphorylation in novel vitamin K analog-induced cell death

S. Osada, B. I. Carr

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In the present study, we show that 2-(2-hydroxyethylsulfaryl)-3-methyl-1,4-naphthoquinone, or CPD 5, is a potent growth inhibitor for pancreas cancer cell lines (ID50: 21.4±3.8, 31.8±2.7 and 55.2±4.5 μM for MiaPaCa, Panc-1 and BxPc3, respectively). It induced protein tyrosine phosphorylation of hepatocyte growth factor (HGF) receptor (c-Met) or epidermal growth factor receptor (EGFR), which increased progressively to a maximum level at 30 min in Panc-1 cells. The receptor phosphorylation by CPD 5 was indicated to be functional, since these receptors were found to bind with Grb2 or SOS1 protein. CPD 5 was also suggested to induce phosphorylation of external signal-regulated kinase (ERK). EGF induced cell proliferation through ERK phosphorylation, since U0126, which is an inhibitor of ERK phosphorylation, abrogated the increase of cyclin D1 by EGF. HGF increased the amount of p27 protein, suggesting that it is associated with cell differentiation. By contrast, U0126 reduced CPD 5-induced cell death. On two-dimensional electrophoresis, we found an extra type of phospho-ERK, and this was completely and selectively abolished by U0126. These results suggest that ERK phosphorylation, especially the extra spot on two-dimensional gel, is critically associated with CPD 5-mediated cell death.

Original languageEnglish
Pages (from-to)1250-1257
Number of pages8
JournalJapanese Journal of Cancer Research
Volume91
Issue number12
Publication statusPublished - 2000

Fingerprint

Vitamin K
Extracellular Signal-Regulated MAP Kinases
Cell Death
Phosphorylation
SOS1 Protein
Epidermal Growth Factor
Proto-Oncogene Proteins c-met
Growth Inhibitors
Hepatocyte Growth Factor
Cyclin D1
Pancreatic Neoplasms
Epidermal Growth Factor Receptor
Tyrosine
Electrophoresis
Cell Differentiation
Proteins
Phosphotransferases
Gels
Cell Proliferation
2-(2-hydroxyethylsulfanyl)-3-methyl-1,4-naphthoquinone

Keywords

  • Extracellular signal-regulated kinase (ERK)
  • Growth inhibition
  • Novel vitamin K analog
  • Pancreas cancer cells
  • Phosphorylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Critical role of extracellular signal-regulated kinase (ERK) phosphorylation in novel vitamin K analog-induced cell death. / Osada, S.; Carr, B. I.

In: Japanese Journal of Cancer Research, Vol. 91, No. 12, 2000, p. 1250-1257.

Research output: Contribution to journalArticle

@article{ec210baa573a47b4b048f7b240e40b93,
title = "Critical role of extracellular signal-regulated kinase (ERK) phosphorylation in novel vitamin K analog-induced cell death",
abstract = "In the present study, we show that 2-(2-hydroxyethylsulfaryl)-3-methyl-1,4-naphthoquinone, or CPD 5, is a potent growth inhibitor for pancreas cancer cell lines (ID50: 21.4±3.8, 31.8±2.7 and 55.2±4.5 μM for MiaPaCa, Panc-1 and BxPc3, respectively). It induced protein tyrosine phosphorylation of hepatocyte growth factor (HGF) receptor (c-Met) or epidermal growth factor receptor (EGFR), which increased progressively to a maximum level at 30 min in Panc-1 cells. The receptor phosphorylation by CPD 5 was indicated to be functional, since these receptors were found to bind with Grb2 or SOS1 protein. CPD 5 was also suggested to induce phosphorylation of external signal-regulated kinase (ERK). EGF induced cell proliferation through ERK phosphorylation, since U0126, which is an inhibitor of ERK phosphorylation, abrogated the increase of cyclin D1 by EGF. HGF increased the amount of p27 protein, suggesting that it is associated with cell differentiation. By contrast, U0126 reduced CPD 5-induced cell death. On two-dimensional electrophoresis, we found an extra type of phospho-ERK, and this was completely and selectively abolished by U0126. These results suggest that ERK phosphorylation, especially the extra spot on two-dimensional gel, is critically associated with CPD 5-mediated cell death.",
keywords = "Extracellular signal-regulated kinase (ERK), Growth inhibition, Novel vitamin K analog, Pancreas cancer cells, Phosphorylation",
author = "S. Osada and Carr, {B. I.}",
year = "2000",
language = "English",
volume = "91",
pages = "1250--1257",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Critical role of extracellular signal-regulated kinase (ERK) phosphorylation in novel vitamin K analog-induced cell death

AU - Osada, S.

AU - Carr, B. I.

PY - 2000

Y1 - 2000

N2 - In the present study, we show that 2-(2-hydroxyethylsulfaryl)-3-methyl-1,4-naphthoquinone, or CPD 5, is a potent growth inhibitor for pancreas cancer cell lines (ID50: 21.4±3.8, 31.8±2.7 and 55.2±4.5 μM for MiaPaCa, Panc-1 and BxPc3, respectively). It induced protein tyrosine phosphorylation of hepatocyte growth factor (HGF) receptor (c-Met) or epidermal growth factor receptor (EGFR), which increased progressively to a maximum level at 30 min in Panc-1 cells. The receptor phosphorylation by CPD 5 was indicated to be functional, since these receptors were found to bind with Grb2 or SOS1 protein. CPD 5 was also suggested to induce phosphorylation of external signal-regulated kinase (ERK). EGF induced cell proliferation through ERK phosphorylation, since U0126, which is an inhibitor of ERK phosphorylation, abrogated the increase of cyclin D1 by EGF. HGF increased the amount of p27 protein, suggesting that it is associated with cell differentiation. By contrast, U0126 reduced CPD 5-induced cell death. On two-dimensional electrophoresis, we found an extra type of phospho-ERK, and this was completely and selectively abolished by U0126. These results suggest that ERK phosphorylation, especially the extra spot on two-dimensional gel, is critically associated with CPD 5-mediated cell death.

AB - In the present study, we show that 2-(2-hydroxyethylsulfaryl)-3-methyl-1,4-naphthoquinone, or CPD 5, is a potent growth inhibitor for pancreas cancer cell lines (ID50: 21.4±3.8, 31.8±2.7 and 55.2±4.5 μM for MiaPaCa, Panc-1 and BxPc3, respectively). It induced protein tyrosine phosphorylation of hepatocyte growth factor (HGF) receptor (c-Met) or epidermal growth factor receptor (EGFR), which increased progressively to a maximum level at 30 min in Panc-1 cells. The receptor phosphorylation by CPD 5 was indicated to be functional, since these receptors were found to bind with Grb2 or SOS1 protein. CPD 5 was also suggested to induce phosphorylation of external signal-regulated kinase (ERK). EGF induced cell proliferation through ERK phosphorylation, since U0126, which is an inhibitor of ERK phosphorylation, abrogated the increase of cyclin D1 by EGF. HGF increased the amount of p27 protein, suggesting that it is associated with cell differentiation. By contrast, U0126 reduced CPD 5-induced cell death. On two-dimensional electrophoresis, we found an extra type of phospho-ERK, and this was completely and selectively abolished by U0126. These results suggest that ERK phosphorylation, especially the extra spot on two-dimensional gel, is critically associated with CPD 5-mediated cell death.

KW - Extracellular signal-regulated kinase (ERK)

KW - Growth inhibition

KW - Novel vitamin K analog

KW - Pancreas cancer cells

KW - Phosphorylation

UR - http://www.scopus.com/inward/record.url?scp=0034518505&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034518505&partnerID=8YFLogxK

M3 - Article

C2 - 11123423

AN - SCOPUS:0034518505

VL - 91

SP - 1250

EP - 1257

JO - Cancer Science

JF - Cancer Science

SN - 1347-9032

IS - 12

ER -