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PMID: 7831333 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cell cycle regulation of metallothionein in human colonic cancer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 2 ·1995-01-17 ·Pages 579-83

Nagel WW, Vallee BL

Abstract

Elevated levels of metallothionein (MT) found in rapidly growing tissues such as neonatal liver and various types of human tumors have suggested a role for MT in cell proliferation. To further explore this possibility we investigated the concentration of MT in human colonic cancer (HT-29) cells at different stages of proliferation by means of immunocytochemistry and competitive binding. MT is increased in subconfluent proliferating cells relative to growth-inhibited confluent cells, much as it is in growing tissues. Cycling cells synchronized with compactin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, revealed an oscillation of cytoplasmic MT that reached a maximum in successive late G1 phases and at the G1/S transition. Individual phase of the cell cycle were assessed by [3H]thymidine incorporation and by immunofluorescence employing an antibody that detects a nuclear antigen associated with proliferation. An enzyme-linked immunosorbent assay was used to quantify the relative amounts of MT in homogenate supernatants of HT-29 cells. A 2- to 3-fold increase in MT in actively proliferating cells and the regulation of the protein during the mitotic cell cycle point to a physiological role for MT in cellular proliferation and suggest that it may also serve as a proliferation marker.

MeSH Terms
Antibodies, Monoclonal Binding, Competitive Cell Cycle/drug effects,physiology Colonic Neoplasms/metabolism Cross Reactions Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Neoplastic Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Immunohistochemistry Lovastatin/analogs & derivatives,pharmacology Metallothionein/immunology,isolation & purification,metabolism Time Factors
Chemicals
Antibodies, Monoclonal Hydroxymethylglutaryl-CoA Reductase Inhibitors mevastatin Metallothionein Lovastatin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Nagel W W
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115.
Vallee B L
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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.92.2.579
Published
1995-01-17
Pages
579-83
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42785
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.2.579 PMC Full Text View journal details
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