Autocrine regulation of erythropoietin gene expression in human hepatocellular carcinoma cells

We have previously reported that a marked increase in erythropoietin (Epo) production can be demonstrated in Hep3B cell cultures in response to hypoxia (1). In order to determine whether this increase involves an autocrine mechanism, we have investigated the effects of purified human recombinant Epo...

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Bibliographic Details
Published in:Life sciences (1973) 1996, Vol.58 (5), p.421-427
Main Authors: Ohigashi, Takashi, Yoshioka, Kunihiko, Fisher, James W.
Format: Article
Language:English
Subjects:
Aerobiosis
autocrine mechanism
Carcinoma, Hepatocellular
Cell Hypoxia
Dose-Response Relationship, Drug
erythropoietin
Erythropoietin - biosynthesis
Erythropoietin - metabolism
Erythropoietin - pharmacology
erythropoietin receptor
Gene Expression Regulation, Neoplastic - drug effects
human hepatocellular carcinoma cells
Humans
Kinetics
Liver Neoplasms
Receptors, Erythropoietin - biosynthesis
Receptors, Erythropoietin - metabolism
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacology
RNA, Messenger - analysis
RNA, Messenger - biosynthesis
Tumor Cells, Cultured
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Summary:We have previously reported that a marked increase in erythropoietin (Epo) production can be demonstrated in Hep3B cell cultures in response to hypoxia (1). In order to determine whether this increase involves an autocrine mechanism, we have investigated the effects of purified human recombinant Epo (rHuEpo) on Epo production. Purified rHuEpo (5–80 mU/ml) produced a significant increase above control levels of Epo in Hep3B cell cultures under normoxic (20% O 2) conditions. Hypoxie (1% O 2) incubation of Hep3B cells with rHuEpo caused an increase over control levels of EpomRNA. Hep3B cells also expressed Epo receptor (Epo-R) transcripts. Binding studies using [ 125I]-Epo revealed that Hep3B cells contain a single class of binding site (kd = 2.9 nmol/rmL and Bmax = 1760 sites/cell). Antierythropoietin receptor monoclonal antibody inhibited the rHuEpo induced elevation in medium levels of Epo and blocked [ 125I]-Epo binding to Hep3B cell membranes. These results demonstrate that the expression of EpomRNA may be controlled, at least in part, by an autocrine mechanism.
ISSN:0024-3205
1879-0631
DOI:10.1016/0024-3205(95)02307-0