The Regulated Expression of Erythropoietin by Two Human Hepatoma Cell Lines

The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. We have screened multiple renal and hepatic cell lines (including MDCK, LLC-PK1, BHK, WRL 68, CLCL, A704, CRFK, A498, ACHN, TCMK-1, LLC-MK2, CaKi-2, HepG2, and Hep3B)...

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Published in:Proceedings of the National Academy of Sciences - PNAS 1987-11, Vol.84 (22), p.7972-7976
Main Authors: Goldberg, Mark A., Glass, G. Allison, Cunningham, James M., Bunn, H. Franklin
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinoma, Hepatocellular - pathology
Cell culture techniques
Cell growth
Cell Line
Cell lines
Cells
Epics
Erythropoietin - biosynthesis
Erythropoietin - genetics
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation
Hep G2 cells
Hepatocytes
Humans
Kidney cells
Kupffer cells
Liver cells
Liver Neoplasms - pathology
Molecular and cellular biology
Molecular genetics
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
RNA, Messenger - biosynthesis
Tumor Cells, Cultured - metabolism
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container_end_page 7976
container_issue 22
container_start_page 7972
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 84
creator Goldberg, Mark A.
Glass, G. Allison
Cunningham, James M.
Bunn, H. Franklin
description The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. We have screened multiple renal and hepatic cell lines (including MDCK, LLC-PK1, BHK, WRL 68, CLCL, A704, CRFK, A498, ACHN, TCMK-1, LLC-MK2, CaKi-2, HepG2, and Hep3B) for either constitutive or regulated expression of Epo. Only the human hepatoma cell lines, Hep3B and HepG2, made significant amounts of Epo as measured both by radioimmunoassay and in vitro bioassay (as much as 330 milliunits per 106 cells in 24 hr). The constitutive production of Epo increased dramatically as a function of cell density in both cell lines. At cell densities < 3.3 × 105 cells per cm2, there was little constitutive release of Epo in the medium (
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With Hep3B cells grown at low cell densities, a mean 18-fold increase in Epo expression was seen in response to hypoxia and a 6-fold increase was observed in response to incubation in medium containing 50 μ M cobalt(II) chloride. At similar low cell densities, Epo production in HepG2 cells could be enhanced an average of about 3-fold by stimulation with either hypoxia or cobalt(II) chloride. Upon such stimulation, both cell lines demonstrated markedly elevated levels of Epo mRNA. 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Psychology ; Gene expression ; Gene Expression Regulation ; Hep G2 cells ; Hepatocytes ; Humans ; Kidney cells ; Kupffer cells ; Liver cells ; Liver Neoplasms - pathology ; Molecular and cellular biology ; Molecular genetics ; Neoplasm Proteins - biosynthesis ; Neoplasm Proteins - genetics ; RNA, Messenger - biosynthesis ; Tumor Cells, Cultured - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1987-11, Vol.84 (22), p.7972-7976</ispartof><rights>1988 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4982-328856cada1456bd8e4c6f2d75963eb40472e67733afad9f0657f165dc3edce43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/84/22.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30583$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30583$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=7481949$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2825172$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goldberg, Mark A.</creatorcontrib><creatorcontrib>Glass, G. 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Psychology</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Hep G2 cells</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Kidney cells</topic><topic>Kupffer cells</topic><topic>Liver cells</topic><topic>Liver Neoplasms - pathology</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Neoplasm Proteins - genetics</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Tumor Cells, Cultured - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goldberg, Mark A.</creatorcontrib><creatorcontrib>Glass, G. Allison</creatorcontrib><creatorcontrib>Cunningham, James M.</creatorcontrib><creatorcontrib>Bunn, H. 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Franklin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Regulated Expression of Erythropoietin by Two Human Hepatoma Cell Lines</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1987-11-01</date><risdate>1987</risdate><volume>84</volume><issue>22</issue><spage>7972</spage><epage>7976</epage><pages>7972-7976</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>The development of a cell culture system that produces erythropoietin (Epo) in a regulated manner has been the focus of much effort. We have screened multiple renal and hepatic cell lines (including MDCK, LLC-PK1, BHK, WRL 68, CLCL, A704, CRFK, A498, ACHN, TCMK-1, LLC-MK2, CaKi-2, HepG2, and Hep3B) for either constitutive or regulated expression of Epo. 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ispartof Proceedings of the National Academy of Sciences - PNAS, 1987-11, Vol.84 (22), p.7972-7976
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1091-6490
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subjects Biological and medical sciences
Carcinoma, Hepatocellular - pathology
Cell culture techniques
Cell growth
Cell Line
Cell lines
Cells
Epics
Erythropoietin - biosynthesis
Erythropoietin - genetics
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation
Hep G2 cells
Hepatocytes
Humans
Kidney cells
Kupffer cells
Liver cells
Liver Neoplasms - pathology
Molecular and cellular biology
Molecular genetics
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
RNA, Messenger - biosynthesis
Tumor Cells, Cultured - metabolism
title The Regulated Expression of Erythropoietin by Two Human Hepatoma Cell Lines
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