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PMID: 8415749 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Tumor necrosis factor-induced c-myc expression in the absence of mitogenesis is associated with inhibition of adipocyte differentiation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 20 ·1993-10-15 ·Pages 9611-5

Ninomiya-Tsuji J, Torti FM, Ringold GM

Abstract

Tumor necrosis factor (TNF) inhibits and reverses differentiation of mouse adipogenic TA1 cells. We have found that TNF induces c-myc in a sustained manner in both preadipocytes and adipocytes; in contrast, serum induces c-myc transiently and only in preadipocytes. This TNF-mediated c-myc induction is not coupled with cell proliferation but is correlated with TNF-mediated inhibition of adipocyte differentiation. We prepared an inducible c-myc transformant of TA1 cells by transfection of the mouse c-myc gene under the control of the metallothionein-I promoter. These cells are unable to differentiate to adipocytes in the presence of Zn2+/Cd2+, and in differentiated TA1 cells, Zn2+/Cd2+ causes reduction of adipocyte-specific gene expression as does TNF. Lastly, exposure of TA1 cells to antisense c-myc oligonucleotide partially blocked the TNF-mediated reduction of adipocyte-specific gene expression. Thus, TNF-mediated c-myc expression is distinct in character from that involved in mitogenic responses but appears to play an important role in inhibition and reversal of adipocyte differentiation.

MeSH Terms
Adipocytes/cytology Base Sequence Cell Differentiation/drug effects Cells, Cultured Gene Expression Regulation/drug effects Genes, fos Genes, jun Genes, myc In Vitro Techniques Mitosis Molecular Sequence Data Oligonucleotides, Antisense Proto-Oncogene Proteins c-myc/physiology RNA, Messenger/genetics Thymidine Kinase/genetics Tumor Necrosis Factor-alpha/pharmacology
Chemicals
Oligonucleotides, Antisense Proto-Oncogene Proteins c-myc RNA, Messenger Tumor Necrosis Factor-alpha Thymidine Kinase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ninomiya-Tsuji J
Affymax Research Institute, Palo Alto, CA 94304.
Torti F M
Ringold G M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.20.9611
Published
1993-10-15
Pages
9611-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC47619
Subset
IM
Grants
NIDDK NIH HHS · DK-42412 · United States
NIGMS NIH HHS · GM-25821 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.20.9611 PMC Full Text View journal details
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