Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells

Qing Mei Wang, Rena Feinman, Fatah Kashanchi, Jean Marie Houghton, George P. Studzinski, Lawrence E. Harrison

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2. colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27(Kip1), leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer.

Original languageEnglish (US)
Pages (from-to)2951-2950
Number of pages2
JournalClinical Cancer Research
Volume6
Issue number7
StatePublished - Jul 1 2000
Externally publishedYes

Fingerprint

Phenylbutyrates
Colonic Neoplasms
S Phase
G1 Phase
Cyclin-Dependent Kinase 2
Cell Differentiation
Cell Cycle
Retinoblastoma Protein
Trans-Activators
Growth
Colorectal Neoplasms
Neoplasms
Phosphotransferases
Phosphorylation
Phenotype
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Wang, Q. M., Feinman, R., Kashanchi, F., Houghton, J. M., Studzinski, G. P., & Harrison, L. E. (2000). Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells. Clinical Cancer Research, 6(7), 2951-2950.
Wang, Qing Mei ; Feinman, Rena ; Kashanchi, Fatah ; Houghton, Jean Marie ; Studzinski, George P. ; Harrison, Lawrence E. / Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 7. pp. 2951-2950.
@article{1283b961da7646eb99ba40cb958ed4bf,
title = "Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells",
abstract = "Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2. colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27(Kip1), leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer.",
author = "Wang, {Qing Mei} and Rena Feinman and Fatah Kashanchi and Houghton, {Jean Marie} and Studzinski, {George P.} and Harrison, {Lawrence E.}",
year = "2000",
month = "7",
day = "1",
language = "English (US)",
volume = "6",
pages = "2951--2950",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

Wang, QM, Feinman, R, Kashanchi, F, Houghton, JM, Studzinski, GP & Harrison, LE 2000, 'Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells', Clinical Cancer Research, vol. 6, no. 7, pp. 2951-2950.

Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells. / Wang, Qing Mei; Feinman, Rena; Kashanchi, Fatah; Houghton, Jean Marie; Studzinski, George P.; Harrison, Lawrence E.

In: Clinical Cancer Research, Vol. 6, No. 7, 01.07.2000, p. 2951-2950.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells

AU - Wang, Qing Mei

AU - Feinman, Rena

AU - Kashanchi, Fatah

AU - Houghton, Jean Marie

AU - Studzinski, George P.

AU - Harrison, Lawrence E.

PY - 2000/7/1

Y1 - 2000/7/1

N2 - Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2. colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27(Kip1), leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer.

AB - Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2. colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27(Kip1), leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer.

UR - http://www.scopus.com/inward/record.url?scp=0005686626&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0005686626&partnerID=8YFLogxK

M3 - Article

C2 - 10914745

AN - SCOPUS:0005686626

VL - 6

SP - 2951

EP - 2950

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 7

ER -

Wang QM, Feinman R, Kashanchi F, Houghton JM, Studzinski GP, Harrison LE. Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells. Clinical Cancer Research. 2000 Jul 1;6(7):2951-2950.