TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells

Young Do Yoo, Ju Youn Choi, Su J. Lee, Jun Suk Kim, Byung R. Min, Young I. Lee, Yoon K. Kang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.

Original languageEnglish
Pages (from-to)512-517
Number of pages6
JournalInternational Journal of Cancer
Volume83
Issue number4
DOIs
Publication statusPublished - 1999 Oct 28

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Cyclin G1
Transforming Growth Factors
Cell Cycle Checkpoints
Stomach
Carcinoma
Stomach Neoplasms
Phosphorylation
Cyclin D
Cyclin E
Cyclins
G1 Phase
S Phase
Cell Cycle
Phosphotransferases
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells. / Yoo, Young Do; Choi, Ju Youn; Lee, Su J.; Kim, Jun Suk; Min, Byung R.; Lee, Young I.; Kang, Yoon K.

In: International Journal of Cancer, Vol. 83, No. 4, 28.10.1999, p. 512-517.

Research output: Contribution to journalArticle

Yoo, Young Do ; Choi, Ju Youn ; Lee, Su J. ; Kim, Jun Suk ; Min, Byung R. ; Lee, Young I. ; Kang, Yoon K. / TGF-β-induced cell-cycle arrest through the p21(WAF1/CIP1)-G1 cyclin/CDKS-p130 pathway in gastric-carcinoma cells. In: International Journal of Cancer. 1999 ; Vol. 83, No. 4. pp. 512-517.
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abstract = "Transforming growth factor-β1 (TGF-β) inhibits cell-cycle progression of many types of cells by arresting them in G1/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-β treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-β also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-β in gastric-cancer cells and that a p21-G1 cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-β in these cells.",
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AU - Lee, Su J.

AU - Kim, Jun Suk

AU - Min, Byung R.

AU - Lee, Young I.

AU - Kang, Yoon K.

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