An N-terminal 78 amino acid truncation of REIC/Dkk-3 effectively induces apoptosis

Biochemical and Biophysical Research Communications
Fernando AbarzuaHiromi Kumon

Abstract

Overexpression of REIC/Dkk-3 (a tumor suppressor gene) induces cancer cell apoptosis through endoplasmic reticulum (ER) stress. Therefore, the identification of the portion of REIC/Dkk-3 that causes ER stress may be essential for the development of cancer treatment based on REIC/Dkk-3. Here, we made several truncated forms of REIC/Dkk-3 and investigated their therapeutic potentials against prostate cancer. Among three truncated forms, a variant comprising the N-terminal 78 amino acid region of REIC/Dkk-3 ((1-78)REIC/Dkk-3) most strongly induced ER stress and apoptosis in human prostate cancer cells (PC3). For in vivo gene expression, we coupled a biodegradable polymer with naked DNA, which attained robust trans-gene expression in PC3-derived subcutaneous tumor. In therapeutic experiments, we demonstrated that multiple direct injections of polymer-conjugated (1-78)REIC/Dkk-3 plasmid provoke ER stress and significantly reduced the subcutaneous tumor volume compared with the control group. We suggest this non-viral strategy may be an effective alternative to viral gene therapy.

References

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Citations

Oct 12, 2011·World Journal of Gastroenterology : WJG·Yu-Mei GuJie Chen
Apr 25, 2012·World Journal of Gastroenterology : WJG·Zi-Rong YangQi-Sheng Liu
Oct 11, 2011·Biochimica Et Biophysica Acta·Jürgen Veeck, Edgar Dahl
Mar 17, 2012·Cell Cycle·Xiao-yan XuHua-chuan Zheng
Aug 13, 2011·Biochemical and Biophysical Research Communications·Kazuhiko OchiaiHiromi Kumon
Apr 14, 2016·Photodiagnosis and Photodynamic Therapy·Hemn Mohammadpour, Reza Fekrazad
Jun 30, 2016·Veterinary and Comparative Oncology·K OchiaiT Omi
Jun 6, 2012·International Journal of Oncology·Takeshi HirataHiromi Kumon

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