TGF-β1 inhibition of apoptosis through the transcriptional up-regulation of Bcl-X(L) in human monocytic leukemia U937 cells

Juhie Lee, Bum Joon Park, Jae Hoon Park, Moon Ho Yang, Sung-Gil Chi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To characterize the TGF-β1 response of monocytic leukemia cells, we analyzed the effects of TGF-β1 on cell proliferation, differentiation, and apoptosis of human monoblastic U937 cells. Treatment of cells with TGF-β1 in the absence of growth factors significantly enhanced cell viability. Flow cytometric analysis of DNA content and CD14 expression revealed that TGF-β1 does not affect cell proliferation and differentiation. Consistent with these results was the finding that no transcriptional induction of Cdk inhibitors such as p21(Waf1), p15(INK4b), and p27(Klp1) was detected following TGF-β1 treatment. Interestingly, however, pretreatment of TGF-β1 significantly inhibited Fas-, DNA damage-, and growth factor deprivation-induced apoptosis. This antiapoptotic effect was totally abrogated by anti-TGF-β1 antibody. Quantitative RT-PCR analysis demonstrated a dose- and time-dependent transcriptional up-regulation of Bcl-X(L), suggesting its implication in the TGF-1-mediated antiapoptotic pathway. We also observed elevated expression of c-Fos and PTEN/MMAC1. But, no detectable change was recognized in expression of c-Jun, Fas, Fadd, Fap-1, Bcl-2, and Bax. Taken together, our study shows that TGF-β1 enhancement of cellular viability is associated with its antiapoptotic effect, which may result from the transcriptional up-regulation of Bcl-X(L).

Original languageEnglish
Pages (from-to)126-133
Number of pages8
JournalExperimental and Molecular Medicine
Volume31
Issue number3
Publication statusPublished - 1999 Sep 30
Externally publishedYes

Fingerprint

U937 Cells
Cell proliferation
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Leukemia
Up-Regulation
Cells
Cell Proliferation
Apoptosis
DNA
DNA Damage
Cell Survival
Polymerase Chain Reaction
Antibodies
kinesin-like protein 1

Keywords

  • Apoptosis
  • Bcl-X(L)
  • Fas
  • PTEN/MMAC1
  • TGF-β1
  • U937

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

TGF-β1 inhibition of apoptosis through the transcriptional up-regulation of Bcl-X(L) in human monocytic leukemia U937 cells. / Lee, Juhie; Park, Bum Joon; Park, Jae Hoon; Yang, Moon Ho; Chi, Sung-Gil.

In: Experimental and Molecular Medicine, Vol. 31, No. 3, 30.09.1999, p. 126-133.

Research output: Contribution to journalArticle

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