인체 위암 세포주에 retroviral vector를 이용한 p53 종양 억제 유전자의 형질도입에 관한 연구
A Study of Retrovirus-mediated p53 Gene Transduction Into Human Gastric Cancer Cell Lines
대한암학회지 1997년 29권 5호 p.754 ~ 764
소속 상세정보
김주항/Joo-Hang Kim
KMID : 0360319970290050754
Abstract
결론
Retrovirus를 이용한 p53 유전자의 형질도입에 의한 위암 세포주의 성장 억제 효과는 p53
유전자의 돌연변이를 함유하고 있는 N-87 위암 세포주에서 뚜렷하였으나 정상형의 p53 유
전자를 가진 YCC-S-2 세포주에서는 성장억제효과가 없었다. 그리고 실험 동물에서 N-87
위암 세포주에 의해 유발된 종괴는 retrovirus를 이용한 P53 유전자의 형질도입으로 종괴의
성장 억제를 관찰할 수 있었으나 정상형의 p53 유전자를 가진 YCC-S-2 세포주에 의해 형
성된 종괴의 성장에는 영향을 미치지 못하였다.
본 연구에서 p53 유전자의 형질도입에 의한 위암 세포주의 성장 억제 효과가 완전하지
않았던 것은 retrovirus를 이용한 유전자의 형질도입시 낮은 형질도입 효율이 주된 원인인
것으로 생각되며, 향후 retrovirus의 감염 효율개선에 관한 연구가 필요하리라고 본다.
#초록#
Purpose : The development of new therapeutic modalities such as gene therapy, which
still requires further investigation, is clearly important to improve the prognosis of
gastric cancer. This study was conducted to evaluate the effect on the growth and the
tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells.
Materials and methods : Human gastric cancer cell lines were cultured and their
DNAs were analyzed to evaluate the p53 status with PCR-SSCP(polymerase chain
reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral
supernatants were obtained from each producer cell line, PA317/LNCX and
PA317/LNC/p53, after construction of retroviral vector LNC/P53 containing human p53
cDNA and producer cell line PA 317/LNC/p53. To investigate the effect of
retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the if vitro
growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and
the YCC-S-2 cell line having wild-type p53 were compared before and after infection
with LNC/p53 retrovirus.
Results : 1%e following results were obtained: 1) The growth inhibition of N-87 cells
after p53 transduction was significant when compared to that of the parent N-87 cells.
The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was
not different. 2) In nude mice, the growth of tumors formed by N-87 cells was
modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However,
the growth of tumors formed by YCC-S-2 cells was not inhibited by
retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after
p53-containing retroviral infection in the KATO-Ⅲ cell lines, which have no p53 gene,
was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with
the m.o.i. of 100 upon immunohistochemical analysis.
Conclusion : The growth inhibition by retrovirus-mediated p53 transduction in human
gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in
vitro, and the growth of tumor masses formed by a gastric cancer cell line having
mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude
mice, although it was not statistically significant. Only modest inhibition of tumor
growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due
to low transduction efficiency.
키워드
Gastric cancer cell; Gene therapy; Retroviral vector; p53 gene;
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