Exp Mol Med.  1999 Sep;31(3):126-133.

TGF-beta1 inhibition of apoptosis through the transcriptional up-regulation of Bcl-X(L) in human monocytic leukemia U937 cells

• Lee JH
• Park BJ
• Park JH
• Yang MH
• Chi SG

Abstract

To characterize the TGF-beta1 response of monocytic leukemia cells, we analyzed the effects of TGF-beta1 on cell proliferation, differentiation, and apoptosis of human monoblastic U937 cells. Treatment of cells with TGF-beta1 in the absence of growth factors significantly enhanced cell viability. Flow cytometric analysis of DNA content and CD14 expression revealed that TGF-beta1 does not affect cell proliferation and differentiation. Consistent with these results was the finding that no transcriptional induction of Cdk inhibitors such as p21Waf1, p15Ink4b, and p27Kip1 was detected following TGF-beta1 treatment. Interestingly, however, pretreatment of TGF-beta1 significantly inhibited Fas-, DNA damage-, and growth factor deprivation-induced apoptosis. This antiapoptotic effect was totally abrogated by anti-TGF-beta1 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-beta1 enhancement of cellular viability is associated with its antiapoptotic effect, which may result from the transcriptional up-regulation of Bcl-X(L).

Keyword

TGF-beta1; U937; apoptosis; Fas; Bcl-XL; PTEN/MMAC1

MeSH Terms

Antigens, CD14/metabolism
Antigens, CD95/metabolism
Apoptosis/drug effects*
Cell Cycle/drug effects
Cell Differentiation/drug effects
Cell Division/drug effects
Cell Survival/drug effects
DNA/analysis
DNA Damage
Gene Expression Regulation, Neoplastic/genetics*
Genes, Suppressor, Tumor/genetics
Human
Leukemia, Myeloid/genetics
Neoplasm Proteins/metabolism
Phosphoric Monoester Hydrolases/genetics
Proto-Oncogene Proteins c-bcl-2/genetics
Proto-Oncogene Proteins c-bcl-2/biosynthesis*
RNA, Messenger/metabolism
Receptors, Antigen, T-Cell/genetics
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transforming Growth Factor beta/pharmacology*
U937 Cells
Up-Regulation (Physiology)