Loss of transferrin receptors following induced differentiation of HL-60 promyelocytic leukemia cells

Yeh, Chang-Jing G.; Papamichael, M.; Faulk, W. Pagé

doi:10.1016/0014-4827(82)90192-6

Cited by 60 publications

(21 citation statements)

References 16 publications

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“…HL-60 cells cultured in 1.25% DMSO exhibit an early decrease in cellular proliferation, followed by differentiation of cells to more mature myeloid forms (20). In addition to these effects, we found that cells exposed to 1.25% DMSO, in agreement with other studies (21,33), showed an associated decrease in surface transferrin receptor. Moreover, when cells were exposed to only 1% DMSO, there was a clear dissociation between relative decreases in transferrin receptor density and decreased cellular proliferation (Fig.…”

Section: Resultssupporting

confidence: 91%

“…The first agent chosen, DMSO, has been studied extensively in the HL-60 cell system, and although the mechanism of action has not been elucidated, cells exposed to DMSO show decreased proliferation followed by terminal myeloid differentiation. Although previous reports have indicated that surface transferrin receptor density on HL-60 cells decreases during DMSO treatment (21,33) and that this decrease may precede by 24 In additional experiments, we studied the effect of agents that we hypothesized would be more specific in affecting transferrin receptor expression. Previous studies have shown that radioactive gallium was taken up avidly by certain tumors (41), and the use of gallium salts as an antitumor agent had been suggested a number of years ago (42).…”

Section: Resultsmentioning

confidence: 99%

“…We have, therefore, studied the well-described human promyelocytic leukemic cell line (HL-60) (19) at various stages of cellular proliferation and during dimethylsulfoxide (DMSO)l induction of differentiation (20,21), in order to measure changes in transferrin receptor by immunoassay techniques and transferrinbinding studies. Our studies indicate that events preceding cell division provide the regulatory stimulus for the synthesis and subsequent appearance of the transferrin receptor on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

Chitambar¹,

Massey²,

Seligman³

1983

J. Clin. Invest.

124

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A B S T R A C T The association of transferrin receptor expression with cellular proliferation has been studied extensively, but a number of events have not been defined. We therefore assayed receptor on promyelocytic leukemia (HL-60) cells at early times after exposure to a stimulus for proliferation (subculture), as well as agents that either induce differentiation (dimethylsulfoxide [DMSO]) or inhibit iron uptake (transferrin-gallium). Within 4 h after subculture, we found that a significant increase in total cellular immunoreactive receptor occurred that preceded by 8 h the increase in cell-surface transferrin binding. Automated fluorocytometric analysis of cells in an immunofluorescent assay indicated that increased surface receptor density appeared on cells in the S, G2, and M phases of the cell cycle. DMSO-treated cells proliferated at the same rate as untreated (control) cells for the first 72 h, but as early as 12 h after treatment transferrin receptor was significantly decreased (65% of control cells). Further decreases occurred at later time points until transferrin receptor was undetectable after 7 d, when proliferation had ceased, cells were arrested in G1 phase of the cell cycle, and myeloid differentiation occurred. After exposure to transferrin-gallium, proliferation ceased, but cells exhibited increased surface receptor and were arrested at S phase of the cell cycle without associated myeloid differentiation.We conclude that events preceding cell division provide the regulatory stimulus for the synthesis and subsequent appearance of the transferrin receptor on the cell surface. Additionally, decreased receptor expression may be important in causing cessation of prolif-

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

Chitambar¹,

Massey²,

Seligman³

1983

J. Clin. Invest.

124

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“…Among the best characterized of these modifications are changes in the expression of the transferrin receptor (TFR), the down regulation of which appears to be involved in the series of programmed events that lead to the termination of proliferation through differentiation to mature cellular forms. Thus, when a variety of leukaemia systems (i.e., M-1, K562, or HL-60 cells) are induced to differentiate to more functionally mature cells by a variety of agents, including dexamethasone, dimethylsulphoxide, butyrate, or retinoic acid, the cell surface expression of the transferrin receptor is significantly reduced as an early event (Schulman et al, 1981;Tei et al, 1982;Testa et al, 1982;Yeh et al, 1982;Felsted et al, 1983;Morin & Sartorelli, 1984).…”

Section: Squamous Cell Carcinoma As a Model Of Blocked Maturationmentioning

confidence: 99%

The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach

Sartorelli¹

1985

Br J Cancer

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it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding which separated termination of proliferation due to cytotoxicity from that caused by maturation.

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“…By contrast, down-regulation of surface transferrinreceptor activity occurs in cells differentiating to a terminal stage, which is thought to be a consequence of cessation of cell proliferation. Examples are the maturation of Friend-virusinfected erythroid cells by erythropoietin (Sawyer & Krantz, 1986), the differentiation of murine erythroleukaemic (MEL) cells in vitro (Mulford & Lodish, 1988) and the differentiation of HL-60 leukaemias (Yeh et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

Modulation of transferrin-receptor activity and recycling after induced differentiation of BeWo choriocarcinoma cells

Ende

Maine

Schwartz

et al. 1990

Biochemical Journal

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BeWo human choriocarcinoma cells normally grow as cytotrophoblast cells. However, in the presence of 100 ,M-forskolin or 5 mM-theophylline, these cells form syncytia similar to morphologically well differentiated syncytiotrophoblasts. We have examined the effect of syncytia formation on transferrin-receptor activity and recycling. Although cellular proliferation stops upon growth in the presence of forskolin or theophylline, the number of cell-surface transferrinreceptors unexpectedly increased 2-fold, whereas the total cellular number increased at most 15 %. The rate of biosynthesis of the transferrin receptor as well as class I MHC glycoprotein did not change measurably during syncytium formation. The biosynthesis of human chorionic gonadotropin increased 35-fold after 30 h of growth in the presence of theophylline. The redistribution of the transferrin receptor in syncytia is maintained by a decreased rate constant of endocytosis (0.141 min-' compared with 0.231 min-' for control cells) and an increased rate constant of externalization (0.122 min-1 compared with 0.060 min-' for control cells). These altered rates of endocytosis and externalization resulted in an increased rate of iron accumulation in the syncytia. Furthermore, the recycling time of the transferrin receptor decreased in cells grown in the presence of theophylline (14.6 min compared with 21.2 min in control cells).

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Loss of transferrin receptors following induced differentiation of HL-60 promyelocytic leukemia cells

Cited by 60 publications

References 16 publications

Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach

Modulation of transferrin-receptor activity and recycling after induced differentiation of BeWo choriocarcinoma cells

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