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Cytokine messenger RNA stability is enhanced in tumor cells
HJ Ross, N Sato, Y Ueyama and HP Koeffler
UCLA Department of Medicine.
Hematopoietic growth factors are produced by a number of human tumors. We
extracted RNA from selected human tumor cells known to produce at least one
hematopoietic growth factor and found high levels of abnormally stable
cytokine messenger (m)RNA. Half-life experiments performed after preventing
RNA synthesis by exposing cells to actinomycin D before RNA extraction
showed stabilization of cytokine messages in tumor cells in liquid culture
as well as in human tumor xenografts grown in mice. Exposure to the phorbol
ester phorbol 12- myristate 13-acetate (TPA) caused enhancement of
granulocyte-macrophage colony-stimulating factor (GM-CSF) message level in
lung cancer cells and in control fibroblasts but elevated levels persisted
far longer in the tumor cells. In normal cells, an AU-rich sequence in the
3' untranslated region of cytokine mRNAs confers lability to the message.
Although a beta-globin gene expression vector containing this region
appears to produce unstable mRNA in lung cancer cells, cytokine mRNAs,
which also contain this sequence, are very stable in the tumors we studied.
This may indicate that another region of the cytokine mRNA molecule is of
greater importance than the AU-rich region in determining mRNA stability in
tumor cells.
Volume 77,
Issue 8,
pp. 1787-1795,
04/15/1991
Copyright © 1991 by The American Society of Hematology
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