Multipotent human hematopoietic cell line K562: Lineage-specific constitutive and inducible antigens

Leary, James F.; Ohlsson‐Wilhelm, Betsy M.; Giuliano, Rita; Labella, Sandra; Farley, Barbara; Rowley, Peter T.

doi:10.1016/0145-2126(87)90065-8

Cited by 55 publications

(39 citation statements)

References 28 publications

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“…The additional low level of expression in thymus suggests expression is limited to only a subpopulation of T cells. Lack of expression in T cells prior to activation and low level expression in K-562 cells, which have been placed within the hematopoietic lineage as multipotent stem cells (Fraser and Berridge, 1987;Leary et al, 1987), suggests further that GRS may not be expressed in early-lineage cells and that expression is limited within the hematopoietic compartment to more di erentiated cell types. However, whether GRS mimics Bcl-2 and is also expressed in the earliest pluripotent stem cells (Veis et al, 1993) is as yet unknown.…”

Section: Melanoma; Fish Analysismentioning

confidence: 99%

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

et al. 1997

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Section: Melanoma; Fish Analysismentioning

confidence: 99%

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

et al. 1997

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“…We examined the expression of HSF2A and HSF2B in K562 myeloprogenitor cells induced along the erythroid lineage by exposure to hemin (37). RT-PCR analysis was used to probe expression of these isoforms with primers designed to produce a 232-bp transcript from HSF2A and a 178-bp transcript from HSF2B.…”

Section: Elevated Activation Of Heat Shock Promoters By Stress In Celmentioning

confidence: 99%

Elevated Expression of Heat Shock Factor (HSF) 2A Stimulates HSF1-induced Transcription during Stress

Soncin

Grammatikakis

et al. 2003

Journal of Biological Chemistry

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Heat shock factor 2 (HSF2) belongs to a family of structurally related transcription factors, which share the property of binding to heat shock elements in the promoters of hsp molecular chaperone genes. However, unlike HSF1, which is essential for hsp gene transcription, the cellular functions of HSF2 are not well known. Here we show that human HSF2, although an ineffective activator of the hsp70 promoter in vitro and in vivo in the absence of stress, participates in the activation of the hsp70 promoter by heat shock. HSF2 was not, however, activated by heat shock in cells deficient in functional HSF1, suggesting a requirement for HSF1 in HSF2-mediated transcriptional enhancement. In addition, HSF2 regulation involves differential activity of two isoforms, HSF2A and HSF2B, which arise from alternative splicing of a common hsf2 gene. Under basal conditions, both HSF2 isoforms are ineffective in activating the hsp70 transcription. However, heat shock differentially activates HSF2A in vivo. This phenomenon appears to be physiologically significant, as human myeloprogenitor cells differentiating along the erythroid lineage express HSF2A de novo and undergo a large increase in capacity to activate the hsp70 promoter. Our experiments further show that HSF1 is physically associated with HSF2 in the cell and that such binding is enhanced by heat shock. Our data suggest a mechanism involving the formation of heterocomplexes between HSF1 and HSF2 with enhanced activity to activate the hsp70 promoter when compared with HSF1 or HSF2 homotrimers.The heat shock transcription factor (HSF) 1 family was first discovered in experiments investigating proteins binding to the promoters of hsp genes (1-3). HSF isolated from yeast, Drosophila, murine, and human cells was shown to be involved in binding to the heat shock response elements (HSE) in heat shock promoters and activating transcription (3-9). Since the isolation of hsf from Saccharomyces cerevisiae, related genes have been found in a wide range of species and a hsf multigene family has now been described (10). Members of the hsf family share structural domains and functional properties including a highly conserved N-terminal DNA binding domain and a heptad repeat "leucine zipper" structure adjacent to the DNA binding domain that regulates trimerization and the ability to bind DNA (10 -12). In mammalian and avian cells, there are multiple hsf family members and four distinct hsf genes have been described to date (6, 7, 13-15). These include heat shock factor 1 (hsf1) with a crucial role in the stress response and other, structurally related genes (hsf2, hsf3, and hsf4) (10, 14 -19).The cellular functions of the hsf2 product still remain largely unknown. Some studies show that HSF2 increases in concentration and becomes activated to a DNA binding form in differentiating K-562 myeloprogenitor cells and that this increase correlates with an increase in transcription of HSP70 (18,19). Although these studies suggest that increases in HSF2 expression may be involved in the activat...

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“…This translocation generates a novel fusion gene, bcr-abl, that encodes a chimeric protein, p210 bcr-abl, the PTK activity of which is aberrantly regulated relative to c-abl (Konopka et al, 1985). K562 cells are regarded as pluripotent hematopoietic progenitor cells expressing markers for erythroid, granulocytic, monocytic, and megakaryocytic lineages as defined by surface-antigen expression (Leary et al, 1987). The K562 cells have been induced to erythroid d i ff e r e n -tiation by the treatment with hemin (Rowley e t a l ., 1981), butyric acid (Cioe et al, 1981), antineoplastic drugs such as Ara-C (Luisi DeLuca et al , 1984), daunomycin (To n i n i et al., 1987), and tiazofurin (Olah e t a l ., 1988), and tyrosine kinase inhibitors (Honma et al , 1989;Honma et al, 1990;Anafi et al , 1993).…”

Section: Introductionmentioning

confidence: 99%

Role of Ras/ERK-dependent pathway in the erythroid differentiation of K562 cells

Kang

Do²,

Kim³

et al. 1999

Exp Mol Med

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The chronic myelogenous leukemic K562 cell line carrying Bcr-Abl tyrosine kinase is considered as pluripotent hematopoietic progenitor cells expressing markers for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Here we investigated the signaling modulations required for induction of erythroid differentiation of K562 cells. When the K562 cells were treated with herbimycin A (an inhibitor of protein tyrosine kinase), r a s antisense oligonucleotide, and PD98059 (a specific inhibitor of MEK), inhibition of ERK/MAPK activity and cell growth, and induction of erythroid differentiation were observed. The r a s mutant, pZIPRas 6 1 l e u -transfected cells, K562-Ras 6 1 l e u , have shown a markedly decreased cell proliferation rate with approximately 2-fold doubling time, compared with the parental K562 cells, and about 60% of these cells have shown the phenotype of erythroid differentiation. In addition, herbimycin A inhibited the growth rate and increased the erythroid differentiation, but did not affect the elevated activity of ERK/MAPK in the K562-Ras 61leu cells. On the other hand, effects of PD98059 on the growth and differentiation of K562-Ras 61leu cells were biphasic. At low concentration of PD98059, which inhibited the elevated activity of ERK/MAPK to the level of parental cells, the growth rate increased and the erythroid differentiation decreased slightly, and at high concentration of PD98059, which inhibited the elevated activity of ERK/MAPK below that of the parental cells, the growth rate turned down and the erythroid differentiation was restored to the untreated control level. Taken together, these results suggest that an appropriate activity of ERK/MAPK is required to maintain the rapid growth and transformed phenotype of K562 cells.

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Multipotent human hematopoietic cell line K562: Lineage-specific constitutive and inducible antigens

Cited by 55 publications

References 28 publications

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

GRS, a novel member of the Bcl-2 gene family, is highly expressed in multiple cancer cell lines and in normal leukocytes

Elevated Expression of Heat Shock Factor (HSF) 2A Stimulates HSF1-induced Transcription during Stress

Role of Ras/ERK-dependent pathway in the erythroid differentiation of K562 cells

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