Growth-inhibitory effect of adenovirus-mediated p53 gene transfer on medulloblastoma cell line, Daoy, harboring mutant p53.
To improve the survival rate, gene therapy, such as the replacement of inactivated tumor suppressor genes, has become a new investigational adjuvant treatment modality for human malignancies. We investigated the effect of adenovirus(Ad)-mediated transfer of wildtype p53 tumor suppressor gene on the medulloblastoma cell line, Daoy, which harbors mutant-type p53 gene. At 50 multiplicity of infection (moi), immunohistochemical staining with p53 monoclonal antibody showed positive staining in all cells 2 days after Ad-CMV-p53 infection. The high expression of wild-type p53 protein was detected in Ad-CMV-p53-infected cells, and expression of wild-type p53 protein peaked on day 2 after the infection. The growth of Ad-CMV-p53-infected cells was greatly suppressed in vitro, and the Ad-CMV-p53 treatment significantly reduced the tumor mass in vivo. The mean weight of Ad-CMV- infected tumors was only 16% of those which were mock infected, and 25% of those which were Ad-CMV-beta-gal infected. On microscopic examination, Ad-CMV-p53-infected tumors showed numerous apoptotic bodies. This Ad-CMV-p53 gene transfer showed high transduction efficacy and expression, resulting in significant growth inhibition of Daoy harboring mutant type p53.
Lee
S H
SH
Laboratory of Cell Biology, Korea Cancer Center Hospital, Seoul. nslsh@mail.kcch.re.kr
Kang
H S
HS
Rhee
C H
CH
Kim
M S
MS
Kwon
H C
HC
Park
M J
MJ
Park
I C
IC
Lee
C T
CT
Kim
C M
CM
Hong
S I
SI
D000260:Adenoviruses, Human / Q000235:genetics*; D015153:Blotting, Western; D002455:Cell Division / Q000235:genetics; D002461:Cell Line, Transformed; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000628:therapy*; D009154:Mutation