Cell cycle arrest and apoptosis induced by SART-1 gene transduction.
The biological function of the SART-1 gene product is demonstrated and its potential as a target for cancer gene therapy is discussed.


METHODS
The SART-1 gene was transduced by a recombinant adenovirus vector and its expression was promoted by a CMV promoter.


RESULTS
The transduction efficiency by recombinant adenoviruses in A549 and MCF-7 cells was determined using a vector expressing luciferase, which showed high expression in the cells. Cell count analysis using Trypan-Blue dye exclusion showed that SART-1 gene transduction inhibited cell growth. Flow cytometry analysis suggested that SART-1 gene transduction induced cell cycle arrest followed by apoptosis. Western blot analysis confirmed that the apoptosis pathway was activated by SART-1 gene transduction.


CONCLUSIONS
These results show that SART-1 gene transduction induces cell cycle arrest leading to apoptosis and suggest the possibility of gene therapy against cancer. In addition, SART-1 is known to be a tumor antigen in a range of cancers recognized by T cells, thus a potential strategy would be the combination of suicide gene therapy with immuno-gene therapy.
Hosokawa
Mami
M
Blood and Stem Cell Transplantation Unit, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.
Kadota
Ritsuko
R
Shichijo
Shigeki
S
Itoh
Kyogo
K
Dmitriev
Igor
I
Krasnykh
Victor
V
Curiel
David T
DT
Takue
Yoichi
Y
Wakasugi
Hiro
H
Takashima
Shigemitsu
S
Heike
Yuji
Y
D000256:Adenoviridae / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000502:physiology; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D009842:Oligopeptides / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics* / Q000502:physiology; D014161:Transduction, Genetic
D000951:Antigens, Neoplasm; D009842:Oligopeptides; D017411:Ribonucleoproteins, Small Nuclear; C431323:SART1 protein, human; C047981:arginyl-glycyl-aspartic acid