| キーワード | splicing, / intron retention, / dystrophin, / antisense chemistry, / rhabdomyosarcoma, / tumor, / tumor suppressor gene, |
|---|
| 研究実績の概要 |
Dystrophin is regarded as a potential tumor suppressor gene because it was shown to be mutated in a variety of rhabdomyosarcoma. Also DMD patients sometimes develop some kind of tumor. Therefore, this project was intended to understand the significance of dystrophin as a tumor suppressor in rhabdomyosarcoma.
In the previous year, the applicants designed an antisense oligonucleotide to alter the splicing of intron 40 retention in rhabdomyosarcoma. They could confirm the abolishment of the intron 40 retention in rhabdomyosarcoma. Also, they observed that the antisense could reduce the growth of rhabdomyosarcoma after 72 hours of incubation. In addition, one carboxyl terminal isoform of dystrophin also showed increase when rhabdomyosarcoma was treated with the antisense.
They also confirmed that this antisense was specific to the cancer-type. They tested in other cancer-types such as colon cancer that showed also retention of intron 40. However, this antisense could not eliminate the intron 40 retention and had no effect on the growth of the colon cancer.
Species specificity was also tested, however, there was no effect on mouse generated cancer cells.
The applicants are now preparing the data for submission.
Finally, the applicants showed that intron retention could be a factor of tumor formation because, growth was reduced after treatment with intron removal agent, antisense oligonucleotide.
|
