Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1

Kevin S. Choe, Farshid Radparvar, Igor Matushansky, Natasha Rekhtman, Xing Han, Arthur I. Skoultchi

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest.

Original languageEnglish (US)
Pages (from-to)6363-6369
Number of pages7
JournalCancer Research
Volume63
Issue number19
StatePublished - Oct 1 2003

Fingerprint

Leukemia, Erythroblastic, Acute
Cell Differentiation
cdc Genes
Erythroblasts
Erythroid Cells
Cell Cycle Checkpoints
Cell Division
Transcription Factors
Cell Culture Techniques
Erythrocytes
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Choe, K. S., Radparvar, F., Matushansky, I., Rekhtman, N., Han, X., & Skoultchi, A. I. (2003). Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. Cancer Research, 63(19), 6363-6369.

Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. / Choe, Kevin S.; Radparvar, Farshid; Matushansky, Igor; Rekhtman, Natasha; Han, Xing; Skoultchi, Arthur I.

In: Cancer Research, Vol. 63, No. 19, 01.10.2003, p. 6363-6369.

Research output: Contribution to journalArticle

Choe, KS, Radparvar, F, Matushansky, I, Rekhtman, N, Han, X & Skoultchi, AI 2003, 'Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1', Cancer Research, vol. 63, no. 19, pp. 6363-6369.
Choe KS, Radparvar F, Matushansky I, Rekhtman N, Han X, Skoultchi AI. Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. Cancer Research. 2003 Oct 1;63(19):6363-6369.
Choe, Kevin S. ; Radparvar, Farshid ; Matushansky, Igor ; Rekhtman, Natasha ; Han, Xing ; Skoultchi, Arthur I. / Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1. In: Cancer Research. 2003 ; Vol. 63, No. 19. pp. 6363-6369.
@article{6c574e340317478c85f61aebb241a6fa,
title = "Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1",
abstract = "Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest.",
author = "Choe, {Kevin S.} and Farshid Radparvar and Igor Matushansky and Natasha Rekhtman and Xing Han and Skoultchi, {Arthur I.}",
year = "2003",
month = "10",
day = "1",
language = "English (US)",
volume = "63",
pages = "6363--6369",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "19",

}

TY - JOUR

T1 - Reversal of tumorigenicity and the block to differentiation in erythroleukemia cells by GATA-1

AU - Choe, Kevin S.

AU - Radparvar, Farshid

AU - Matushansky, Igor

AU - Rekhtman, Natasha

AU - Han, Xing

AU - Skoultchi, Arthur I.

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest.

AB - Oncogenic transformation usually inhibits normal cell differentiation processes. Certain chemical agents can force some tumor cells to resume their differentiation program and undergo cell cycle arrest, an approach termed differentiation therapy. Mouse erythroleukemia (MEL) cells represent an important cell culture model system for investigating the principles of differentiation therapy. MEL cells are malignant erythroblasts that are blocked from differentiating into mature erythroid cells because of inappropriate expression of the transcription factor PU.1, which binds to and represses GATA-1, a key transcriptional stimulator of red blood cell differentiation. We report here that the block to differentiation in MEL cells can be overcome by providing the cells with additional GATA-1. A conditionally active form of GATA-1 can trigger the cells to differentiate, undergo terminal cell division, and lose their tumorigenicity. We also show that the gene for the cell cycle inhibitor p21 is transcriptionally regulated by GATA-1 and is a likely downstream effector of GATA-1 that helps to promote differentiation and proliferation arrest.

UR - http://www.scopus.com/inward/record.url?scp=0141953999&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141953999&partnerID=8YFLogxK

M3 - Article

VL - 63

SP - 6363

EP - 6369

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 19

ER -