Down-regulation of Telomerase Activity Is an Early Event in the Differentiation of HL60 Cells

Savoysky, Ericka; Yoshida, Kenji; Ohtomo, Toshihiko; Yamaguchi, Yohsuke; Akamatsu, Ken‐ichi; Yamazaki, Taeko; Yoshida, Shonen; Tsuchiya, Masayuki

doi:10.1006/bbrc.1996.1356

Cited by 80 publications

(54 citation statements)

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“…Telomerase then decreases as GC cells transition to memory cells. Plasma cells, which are terminally differentiated cells, expressed moderate levels of telomerase, thus differing from previous observations of other terminally differentiated cells (61)(62)(63). The telomerase RNA component was regulated in parallel with telomerase activity in tonsil B cell subsets both in vivo and in vitro.…”

Section: Discussioncontrasting

confidence: 99%

“…The expression of telomerase in these somatic cells appears to be generally down-regulated during in vivo development and differentiation, as demonstrated in hematopoietic progenitor cells (30) and T cells (33) and during the induction of differentiation in the promyelocytic cell line HL60 in vitro (61)(62)(63). A low to undetectable level of telomerase activity has been reported in peripheral blood B cells (29,32), and a high level in tonsil GC cells (31,34).…”

Section: Discussionmentioning

confidence: 98%

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Telomere lengthening and telomerase activation during human B cell differentiation

Weng

Granger²,

Hodes³

1997

Proc. Natl. Acad. Sci. U.S.A.

253

226

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The function of the immune system is highly dependent on cellular differentiation and clonal expansion of antigen-specific lymphocytes. However, little is known about mechanisms that may have evolved to protect replicative potential in actively dividing lymphocytes during immune differentiation and response. Here we report an analysis of telomere length and telomerase expression, factors implicated in the regulation of cellular replicative lifespan, in human B cell subsets. In contrast to previous observations, in which telomere shortening and concomitant loss of replicative potential occur in the process of somatic cell differentiation and cell division, it was found that germinal center (GC) B cells, a compartment characterized by extensive clonal expansion and selection, had significantly longer telomeric restriction fragments than those of precursor naive B cells. Furthermore, it was found that telomerase, a telomeresynthesizing enzyme, is expressed at high levels in GC B cells (at least 128-fold higher than those of naive and memory B cells), correlating with the long telomeres in this subset of B cells. A hallmark of the immune system is its ability to respond effectively to the constantly changing antigenic and pathogenic challenges in its environment. In the case of antibody-mediated humoral responses, this ability is achieved by the existence of a diverse repertoire of naive B cells and by an adaptive process that allows extensive receptor diversification by somatic hypermutation, clonal expansion, and selection to generate optimized binding affinity of antibody to antigen (1). B lymphocytes derive from bone marrow progenitor cells and undergo an ordered sequence of differentiation with phenotypically distinct stages during lineage development and during activation of an immune response (2). During T cell-dependent immune responses, mature antigennaive B lymphocytes differentiate in a unique germinal center (GC) environment into GC B cells, then to memory B cells or plasma cells (3). In the GC, substantial cell division occurs during a differentiation process that comprises several important processes, including somatic hypermutation of variable domains of immunoglobulin (Ig) genes (4-6), clonal selection of mutated antibody-producing B cells with high antigen-binding affinity (7), and Ig isotype switching (8). In recent years, substantial progress has been made in understanding the process of Ig variable gene rearrangement, the structure and function of GCs, and the phenotypic changes that occur in the transition of immature to mature B cells, and of naive B cells to GC to memory or plasma cells. However, less is known about the mechanisms underlying the replicative lifespan of lymphocytes and immunologic memory.Telomerase and the regulation of telomere length have recently drawn considerable attention for their potential roles in critical biological functions, including the control of cellular replication (9). Telomeres are specialized terminal chromosomal structures that consist of tandem hex...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Telomere lengthening and telomerase activation during human B cell differentiation

Weng

Granger²,

Hodes³

1997

Proc. Natl. Acad. Sci. U.S.A.

253

226

View full text Add to dashboard Cite

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“…HPr-1 cells were negative for AR expression. cell lines (Sharma et al 1995), as well as in some carcinoma cell lines (Savoysky et al 1996). To further demonstrate that HPr-1AR cells were undergoing differentiation, telomerase activity in HPr-1AR cells grown in the presence or absence of androgen was determined by the TRAP assay.…”

Section: Telomerase Activitiesmentioning

confidence: 99%

“…PSA, on the other hand, is another important biochemical marker of prostate epithelial cells (Sinha et al 1986, Fong et al 1991. It is expressed mainly in differentiated secretory cells and is androgen dependent (Wolf et al 1992, Savoysky et al 1996. The up-regulation of cytokeratins K8 and K18, together with the induction of PSA transcript in HPr-1AR cells during androgen treatment provided strong evidence that the cells were undergoing differentiation under the influence of androgen.…”

Section: Hpr-1mentioning

confidence: 99%

Androgen induces differentiation of a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line

Ma¹,

Chan²,

Choo³

2001

Journal of Endocrinology

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Androgen signaling is crucial for the growth and development, as well as for tumorigenesis of the prostate. However, many of the prostate epithelial cell lines developed previously, either normal or tumorigenic, do not express androgen receptor (AR) or respond to androgen. In order to advance our understanding on how androgen signaling regulates the growth and the differentiation status, and affects tumorigenicity of the epithelial cell, we performed experiments on HPr-1, a prostate cell line recently immortalized from normal human prostate epithelial cells. In the present study, AR was stably transfected into HPr-1 cells by replication-defective retrovirus. Treatment of HPr-1AR cells with androgen resulted in cell differentiation and growth retardation accompanied with up-regulation of cytokeratins K8 and K18, prostate specific antigen, p21 and p27, and down-regulation of c-myc, bcl-2 and telomerase activity. Our results suggest that androgen promotes the process of differentiation in a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line which may reflect the normal effects of androgen on prostate cells.

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“…25) One of the possible functions of the induction of p21 is to block the cell cycle in the G 1 state, leading to the differentiation of HL-60 cells. In the differentiation of HL-60 induced with ATRA, the induction of p21 mRNA was reported 27) to be coupled with the differentiation. Therefore, cyclin-dependent kinase or its inhibitor may be a candidate that regulates NF-TS3, which suppresses the expression of the human TS gene, a typical essential gene for cellular proliferation.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Nuclear Factors that Bind to the Human Thymidylate Synthase Gene in HL-60 Cells Differentiated by All-trans Retinoic Acid Treatnent.

Horie

Komada

Ueta

et al. 2001

Biological & Pharmaceutical Bulletin

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Thymidylate synthase (TS; N 5 ,N 10 -methylenetetrahydrofolate: dUMP C-methyltransferase; EC 2.1.1.45) catalyzes the conversion of deoxyuridylate to thymidylate, and is a key enzyme that controls a balanced supply of four DNA precursors. The gene for TS is a typical housekeeping gene and its expression is regulated depending on both the cell cycle [1][2][3] and the state of cell proliferation.4-7) The human TS gene and its cDNA were isolated [8][9][10][11] and their primary and functional structures have been extensively elucidated.

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Down-regulation of Telomerase Activity Is an Early Event in the Differentiation of HL60 Cells

Cited by 80 publications

References 0 publications

Telomere lengthening and telomerase activation during human B cell differentiation

Telomere lengthening and telomerase activation during human B cell differentiation

Androgen induces differentiation of a human papillomavirus 16 E6/E7 immortalized prostate epithelial cell line

Characterization of Nuclear Factors that Bind to the Human Thymidylate Synthase Gene in HL-60 Cells Differentiated by All-trans Retinoic Acid Treatnent.

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