Carbon dioxide, hypoxia and low pH lead to overexpression of c-myc and HMGB-1 oncogenes in neuroblastoma cells.
OBJECTIVE
It has been reported that CO (2) gas, used to establish a pneumoperitoneum during laparoscopy, affects the behavior of tumor cells. The proto-oncogenes C-MYC and HMGB-1 mediate aggressive behavior of neuroblastomas. We studied whether exposure to CO (2), hypoxia or acidosis affects the expression of C-MYC and HMGB-1 in neuroblastoma cells.


METHODS
SH-SY5Y cells were incubated with 100% CO (2), 95% helium/5% CO (2) or pH 6.2 for 2 h. The expression of C-MYC and HMGB-1 was measured by Western blot test immediately, 3 h and 6 h after incubation. Additionally, we measured apoptosis after incubation using fluorometric measurements of caspase 3 and 7 activity.


RESULTS
C-myc (160+/-26%, p=0.007 and 138+/-16% vs. control, p=0.04) and HMGB-1 proteins (140+/-13% and 136+/-11%, both p=0.037) were found to be significantly upregulated 6 h after incubation with CO (2) and helium. There was early upregulation of both oncogenes 3 h after CO (2) incubation (251+/-79%, p=0.04 and 292+/-136, p=0.037). Correspondingly, pH 6.2 led to significant overexpression. Levels of apoptosis were reduced.


CONCLUSIONS
Exposures mimicking conditions of CO (2) pneumoperitoneum lead to significant overexpression of C-MYC and HMGB-1 in neuroblastoma cells with decreased apoptosis. These results point to a negative influence and potentially increased malignancy of tumor cells.
Reismann
M
M
Department of Pediatric Surgery, Medical School Hannover, Hannover, Germany. reismann.marc@mh-hannover.de
Wehrmann
F
F
Schukfeh
N
N
Kuebler
J F
JF
Ure
B
B
Glüer
S
S
D000138:Acidosis / Q000378:metabolism*; D002245:Carbon Dioxide / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D024243:HMGB1 Protein / Q000096:biosynthesis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology
D024243:HMGB1 Protein; D002245:Carbon Dioxide