Dp. Heruth et al., SODIUM-BUTYRATE CAUSES AN INCREASE IN THE BLOCK TO TRANSCRIPTIONAL ELONGATION IN THE C-MYC GENE IN SW837 RECTAL-CARCINOMA CELLS, The Journal of biological chemistry, 268(27), 1993, pp. 20466-20472
Elevated expression of the c-myc oncogene is a frequent finding in tum
ors and cell lines derived from carcinomas of the colon and rectum. In
a previous study we demonstrated that the differentiation agent sodiu
m butyrate causes a rapid reduction in the expression of c-myc RNA in
the rectal carcinoma cell line SW837. This effect was blocked by inhib
itors of protein synthesis, suggesting that butyrate causes the induct
ion of an activity that has a negative effect on c-myc expression In t
he present work we demonstrate that the rapid decrease in the level of
c-myc RNA, upon treatment of SW837 cells with 2 mM butyrate, is follo
wed by a slower decrease in the level of p53 RNA and an increase in th
e RNA levels for fibronectin and a placental type alkaline phosphatase
. Using in vitro elongation of nascent transcripts to measure transcri
ption and actinomycin D chase experiments to measure RNA stability, we
show that the reduction in expression of c-myc RNA is due to an incre
ase in the block to transcriptional elongation, rather than a decrease
in transcriptional initiation or an increase in degradation of the RN
A. We conclude that sodium butyrate induces an activity that increases
the transcriptional block in SW837 cells, and that regulation of tran
scriptional elongation is an important mechanism for regulating c-myc
expression in this cell type. A shift in relative usage of the two maj
or promoters in the c-myc gene accompanies the reduction in expression
. The potential significance of this finding with respect to transcrip
tional elongation is discussed. Mutations in the exon 1/intron 1 bound
ary region of the c-myc gene cause an increase in transcriptional elon
gation in Burkitt lymphoma. We sequenced this region in a series of ce
ll lines derived from colorectal carcinomas, all of which had an eleva
ted level of c-myc expression, to determine if a similar mutational me
chanism is at work in this disease. All of the lines examined had a no
rmal c-myc DNA sequence, suggesting that the deregulation of c-myc exp
ression in colon cancer is not due to a cis mutation in this region.