Latent form of transforming growth factor-β1 acts as a potent growth inhibitor on a human erythroleukemia cell line

Piao, Yun-Song; Ichijo, Hidenori; Miyagawa, Kiyoshi; Ohashi, Hideya; Takaku, Fumimaro; Miyazono, Kohei

doi:10.1016/0006-291x(90)91725-8

Cited by 23 publications

(16 citation statements)

References 18 publications

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“…Latent TGF-f circulates in plasma at concentrations well above those necessary for TGF-f to elicit biological activity (Danielpour et al, 1989 (Knabbe et al, 1987;Glick et al, 1989;Oreffo et al, 1989;Colletta et al, 1990;Twardzik et al, 1990;Flaumenhaft et al, unpublished data). Activation of latent TGF-#1 also occurs in homotypic cultures of erythroleukemia cell lines (Piao et al, 1990) (Jullien et al, 1989;Pfeilschifter et al, 1990). However, it is difficult to conceive of how such a process would be controlled and how the mature growth factor would be released into the extracellular milieu.…”

Section: Regulation In Time and Spacementioning

confidence: 99%

The extracellular regulation of growth factor action.

Flaumenhaft

Rifkin

1992

MBoC

163

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Section: Regulation In Time and Spacementioning

confidence: 99%

The extracellular regulation of growth factor action.

Flaumenhaft

Rifkin

1992

MBoC

163

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“…There is abundant data regarding the effects of TGF-b on leukemic cells lines, which range from inhibition of proliferation and induction of differentiation, to altered expression of adhesion molecules and cytokine receptors, and the induction of apoptosis. [61][62][63] In general, these studies suggest that, in most hematopoietic malignancies, essential components of the TGF-b signaling pathway are indeed expressed and can at a minimum transduce transcriptional responses, even in the absence of the ability to induce a complete growth arrest or initiate an apoptotic response.…”

Section: Mutational Inactivation Of the Tgf-b Signaling Pathway Uncommentioning

confidence: 99%

Transforming growth factor-β signaling in normal and malignant hematopoiesis

Letterio

2003

Leukemia

123

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Transforming growth factor-b (TGF-b) is perhaps the most potent endogenous negative regulator of hematopoiesis. The intracellular signaling events mediating the effects of TGF-b are multiple, involving extensive crosstalk between Smad-dependent and MAP-kinase-dependent pathways. We are only beginning to understand the importance of the balance between these cascades as a determinant of the response to TGF-b, and have yet to determine the roles that disruption in TGF-b signaling pathways might play in leukemogenesis. This review summarizes current knowledge regarding the function of TGF-b in normal and malignant hematopoiesis. The principal observations made by gene targeting studies in mice are reviewed, with an emphasis on how a disruption of this pathway in vivo can affect blood cell development and immune homeostasis. We overview genetic alterations that lead to impaired TGF-b signaling in hematopoietic neoplasms, including the suppression of Smad-dependent transcriptional responses by oncoproteins such as Tax and Evi-1, and fusion proteins such as AML1/ETO. We also consider mutations in genes encoding components of the core cell cycle machinery, such as p27 Kip1 and p15INK4A , and emphasize their impact on the ability of TGF-b to induce G1 arrest. The implications of these observations are discussed, and opinions regarding important directions for future research on TGF-b in hematopoiesis are provided.

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“…There are abundant data concerning the effects of TGF-β on leukemia cells lines, including the inhibition of proliferation, induction of differentiation, altered expression of adhesion molecules and cytokine receptors, induction of apoptosis (27)(28)(29) and its acting as an inhibitory autocrine factor in the proliferation of leukemia cells (30). TGF-β1 is thought to be a primary negative regulator of early hematopoiesis (31,32).…”

Section: Discussionmentioning

confidence: 99%

Effect of TGF-β on Gli2 expression in HL60 and U937 cell lines

Pan

2012

Mol Med Report

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Abstract. The Hedgehog (Hh) signaling pathway is involved in a variety of tumor-related diseases, including leukemia. The aim of this study was to determine whether there is an interaction between the Hh signaling pathway and transforming growth factor-β (TGF-β) in the HL60 and U937 cell lines. HL60 and U937 cells were treated with TGF-β, tumor necrosis factor-α (TNF-α) and specific inhibitor of Smad3 (SIS3). The expression of Gli2 was detected by real-time PCR and western blotting. The results showed that TGF-β alone did not affect the Gli2 expression in HL60 cells, while it significantly reduced the level of Gli2 expression in U937 cells. TGF-β+TNF-α reduced the expression of Gli2 in HL60 cells and U937 cells. The reduction in the level of Gli2 expression in U937 cells by TGF-β+TNF-α was greater than that caused by TGF-β alone. SIS3 inhibited the effect of TGF-β. Our results suggest that the effect on Gli2 expression in HL60 and U937 cells induced by TGF-β is Smad3-dependent and independent of Hh receptor signaling. IntroductionThe Hedgehog (Hh) signaling pathway is associated with cell growth and differentiation, with a normal role in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth (1). Gli transcription factors are the final effectors of the Hh signaling pathway. In a number of tumors, including those of the pancreas, prostate, skin and lung, the ectopic activation of Gli proteins has been linked to tumorigenesis (2). Evidence suggests additional, non-canonical mechanisms of Gli activation (2). Certain studies have suggested that in normal fibroblasts and keratinocytes, as well as in various cancer cell lines, the Gli transcription factors are not solely regulated by Hh/Smo signaling, but also by other pathways, including the transforming growth factor-β (TGF-β) signaling pathway. TGF-β induces Gli2 expression in a Smad3-dependent manner and this effect is independent from the Patched/Smoothened (Ptch/Smo) axis (3).In hematopoiesis, Hh family members are also significant in the regulation of stem/progenitor cell expansion in vitro and in vivo (4). The components of Hh signaling have been detected in several leukemia cell lines; Ptch and Smo were expressed in Jurkat cells (5), Shh and Gli1 in HL60 and KG-1 cells (6) and Gli2 in U937 and HL60 cells (7). Similar to Hh members, TGF-β is involved in regulating the balance between proliferation and differentiation in hematopoietic cells (8,9).To find a new target for leukemia treatment, we hypothe sized that there is also crosstalk between the Hh signaling pathway and TGF-β in leukemia cells. In this study, we examined the ability of TGF-β to modulate the expression of the Hh signaling molecule Gli2 in the HL60 and U937 cell lines. Targeting the interaction between Hh and TGF-β signaling may provide new therapeutic opportunities for leukemia treatment. Materials and methodsCell cultures and reagents. The human myeloid leukemia cell lines HL60 and U937 were gifts from the Institute of Hematology (Chine...

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Latent form of transforming growth factor-β1 acts as a potent growth inhibitor on a human erythroleukemia cell line

Cited by 23 publications

References 18 publications

The extracellular regulation of growth factor action.

The extracellular regulation of growth factor action.

Transforming growth factor-β signaling in normal and malignant hematopoiesis

Effect of TGF-β on Gli2 expression in HL60 and U937 cell lines

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