Regulation of cell growth and the c-myc proto-oncogene expression by phorbol ester 12-0-tetradecanoyl phorbol-13-acetate (TPA) in the androgen-independent human prostatic JCA-1 cells.
The proliferation of the human prostatic cancer JCA-1 cells showed a complex response to different concentrations of TPA. Whereas cells exposed for 24 h had growth reduction which was proportional to the concentration of TPA added to the culture media, they showed resistance to low (0.016 and 0.16 nM) but not high (> or = 1.6 nM) doses of TPA after 72 h. Growth-inhibited, treated cells also displayed a distinct cell morphology compared with the controls. Since c-myc expression has previously been shown to be correlated with cellular proliferation, we determined changes in its steady-state level in control and treated cells by Northern analysis. Following a 24h, 48h, and 72h treatment, with 16 nM TPA, c-myc mRNA was suppressed by 91%, 83%, and 78%, respectively, in good agreement with the extent of growth reduction observed. At the low dose of TPA (0.16 nM), however, the c-myc mRNA expression remained inhibited by 85% even though cell growth was only reduced by 10-14%. No difference in the total amount of c-myc protein could be detected between control and treated cells by Western analysis.
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595.
X H
XH
Wang
C A
CA
Whyzmuzis
S
S
An
Y
Y
Chen
J M
JM
Wu
T A
TA
Schneidau
C
C
Mallouh
H
H
Tazaki
D000728:Androgens / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D016259:Genes, myc; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D018076:DNA, Complementary; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate