Transient Reduction of PTI-1 Expression by Short Interfering RNAs Inhibits the Growth of Human Prostate Cancer Cell Lines

Transient Reduction of PTI-1 Expression by Short Interfering RNAs Inhibits the Growth of Human Prostate Cancer Cell Lines

LEI YU,^* GUOJUN WU,^* LIGUO WANG,^* HE WANG and GENG ZHANG

Department of Urology, Xi-jing Hospital, the Fourth Military Medical University, Xi'an, China

The prostate tumor-inducing gene 1 (PTI-1) was originally identified by differential ribonucleic acid (RNA) display in human prostate carcinoma. PTI-1 is expressed in human prostate carcinoma but not in benign prostate hypertrophy or normal prostate tissue. PTI-1 may be a member of oncogenes that could affect protein translation and contribute to carcinoma development in human prostate. To investigate the role of PTI-1 in human prostate carcinoma, we constructed three different short interfering RNA (siRNA) vectors (pSilencer3.1-neo-Yu Lei [YL]1-2, -YL3-4 and -YL5-6), each of which was transfected into DU145 and PC3 human prostate cancer cell lines. Among these siRNAs, only pSilencer3.1-neo-YL1-2 could almost completely block the expression of PTI-1 in these two cell lines. The growth of the cell lines was then evaluated after transfection. The proliferation rate was retarded in DU145 and PC3 cells transfected with pSilencer3.1-neo-YL1-2, compared with the cells transfected with a control vector; namely, about 88.6% of DU145 and 80.2% of PC3 cancer cells were blocked at the G1 phase when transfected with pSilencer3.1-neo-YL1-2, compared to 62.0% in DU145 cells and 51.7% in PC3 cells, transfected with the control vector. Moreover, 68.3% of DU145 cells and 72.3% of PC3 cells were induced into apoptosis, while in control transfection, the population was 26.6% in DU145 cells and 28.4% in PC3 cells. These results indicate that blocking PTI-1 expression can inhibit the growth of certain prostate cancer cell lines. We suggest that PTI-1 may serve as a target for the gene-based therapy of human prostate carcinoma.

keywords —— PTI-1; siRNA; prostate carcinoma; cell growth; gene therapy

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Tohoku J. Exp. Med., 2006, 209, 141-148

Correspondence: Lei Yu, Department of Urology, Xi-jing Hospital, the Fourth Military Medical University, Xi'an, 710032, China.

e-mail: yulei1@fmmu.edu.cn
^*These three authors contributed equally to this work.