Objective To investigate the effects of retinoic acid ( RA) on the growth,
morphology, oncogene expression and regulation of nasopharyngeal carcinoma
cells.
Methods Nasopharyngeal carcinoma cell line (HNE1) was induced by RA. The HA
-treated and control cells were established and cellular morphology and gro
wth patterns were defined. Oncogene expression and regulation were detected
by Northern hybridization and DNase-I hypersensitive site analysis.
Results RA markedly inhibited cell growth. The growth of HNE1 cells was red
uced to 50% of the control level on the 4th day of RA (10(-4)mol/L) treatme
nt. After 4 days of treatment, the rapidly growing polygonal cells were rev
ersed into a slow growing phenotype, with flattened morphology similar to f
ibroblast-like cells. Northern hybridization showed that c-myc and c-Ha-ras
expression was high in HNE1 cells and undetectable in normal blood cells.
c-myc was down-regulated at 48 h of RA treatment. In contrast, the c-Ha-ras
was not affected. DNase I hypersensitive site analysis detected changes in
the regulatory elements of c-myc and c-Ha-ras genes. 5 hypersensitive site
s were found in the c-myc of HNE1 cells, while 3 hypersensitive sites disap
peared upon HNE1 induction. However, only 1 hypersensitive site was found i
n c-Ha-ras of RA treated cells and controls. In normal peripheral white blo
od cells, no DNase I hypersensitive sites were found in the inactive c-myc
and c-Ha-ras gene.
Conclusion RA can induce differentiation in a nasopharyngeal carcinoma cell
line at high concentration or RA; HNE1 snows some similar patterns of DNas
e I hypersensitive sites with the common one in other types of cells expres
sing c-myc. The repression of c-myc expression with induction is accompanie
d by the loss of 3 DNase- I hypersensitive sites; c-myc has more than one i
nactive conformation.