Treatment efficiency of a suicide gene therapy using prostate‐specific membrane antigen promoter/ enhancer in a castrated mouse model of prostate cancer

• Published in: Cancer science Vol. 95; no. 4; pp. 367 - 370
• Main Authors: Ikegami, Shusei, Tadakuma, Takushi, Ono, Takeshi, Suzuki, Satoshi, Yoshimura, Ichiro, Asano, Tomohiko, Hayakawa, Masamichi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2004; Blackwell; John Wiley & Sons, Inc
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - therapy; Androgens; Animals; Antigens; Antigens, Surface - genetics; Biological and medical sciences; Castration; Enhancer Elements, Genetic - genetics; Gene therapy; Genes, Reporter; Genes, Transgenic, Suicide; Genetic Therapy; Genetic Vectors - genetics; Glutamate Carboxypeptidase II - genetics; Growth inhibition; Gynecology. Andrology. Obstetrics; Herpesvirus 1, Human - genetics; Humans; Kinases; Liposomes; Luciferases - genetics; Male; Male genital diseases; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Nephrology. Urinary tract diseases; Orchiectomy; Promoter Regions, Genetic - genetics; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - therapy; Suicide; Suicide genes; Thymidine; Thymidine kinase; Thymidine Kinase - genetics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Xenograft Model Antitumor Assays; Animal model; Urinary system disease; Prostate disease; Transcription promoter; Treatment efficiency; Rodentia; Malignant tumor; Suicide gene; Vertebrata; Mammalia; Treatment; Mouse; Prostate specific membrane antigen; Gene therapy; Male genital diseases; Prostate cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2004.tb03217.x

Suicide gene therapy has potential for the treatment of prostate cancer under conditions of androgen deprivation. We show here that the combination of promoter/enhancer of prostate‐specific membrane antigen (PEPM) and the Cre‐loxP system is a good method to express a suicide gene, namely herpes virus thymidine kinase (TK), in prostate cancer cells. We have examined this system in a castration model in vivo, in comparison with a prostate‐specific antigen promoter/enhancer system (PP). In the castrated mice, the tumor luciferase activity with the combination of the PEPM plus the Cre‐loxP system was about 50 times greater than that with the control GL3 plasmid. A similar increase was observed in non‐castrated mice. In contrast, the luciferase activity of the plasmid PP was decreased significantly in tumors from castrated mice as compared with tumors from non‐castrated control mice. Regarding the therapeutic effect, the combination plasmid PEPM‐Cre plus CMV‐loxP‐TK exhibited a strong inhibitory effect on tumor growth in the castrated mice, as in the non‐castrated mice. In contrast, PP‐TK plasmid did not show any significant growth inhibition in the castrated mice. These findings indicate that the combination of PEPM and Cre‐loxP system may have a good treatment effect under androgen ablation conditions in vivo, and our system may therefore be applicable to patients who have previously received androgen deprivation therapy.