Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone–releasing hormone agonist

• Published in: Cancer science Vol. 97; no. 6; pp. 459 - 467
• Main Authors: Said, Mahmoud M., Hokaiwado, Naomi, Tang, Mingxi, Ogawa, Kumiko, Suzuki, Shugo, Ghanem, Hala M., Esmat, Amr Y., Asamoto, Makoto, Refaie, Fawzia M., Shirai, Tomoyuki
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01-06-2006; Blackwell
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Androgen-Binding Protein - genetics; Animal tumors. Experimental tumors; Animals; Animals, Genetically Modified; Antigens, Polyomavirus Transforming - genetics; Antineoplastic agents; Antineoplastic Agents, Hormonal - pharmacology; Biological and medical sciences; Chemotherapy; Experimental genital and mammary tumors; Follicle Stimulating Hormone - blood; Gonadotropin-Releasing Hormone - agonists; Immunohistochemistry; Leuprolide - pharmacology; Luteinizing Hormone - blood; Luteinizing Hormone - drug effects; Male; Medical sciences; Oligonucleotide Array Sequence Analysis; Original; Pharmacology. Drug treatments; Prostate - drug effects; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Rats; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Seminal Vesicles - drug effects; Simian virus 40; Testosterone - blood; Tumors; Antineoplastic agent; Agonist; Chemoprophylaxis; Peptides; Prostate disease; Rat; Gonadotropin RH; Nonapeptide; Papovaviridae; Carcinogenesis; Prevention; Cancerology; Hormone releasing factor; Male genital diseases; Leuprorelin; Urinary system disease; Polyomavirus; Rodentia; Malignant tumor; Simian virus 40; Hypothalamic hormone; Virus; Vertebrata; Mammalia; Adenohypophyseal hormone; Analog; Animal; T antigen; Prostate cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2006.00213.x

The effects of leuprorelin acetate, a luteinizing hormone‐releasing hormone agonist (LHRH‐A), on prostate carcinogenesis in probasin/SV40 Tag transgenic rat was investigated. Fifteen weeks after administration of 0.28 and 2.8 mg/kg leuprorelin, prostate weights and serum testosterone levels were significantly decreased compared to values for transgenic controls. Histopathological findings revealed that the incidence of prostatic adenocarcinomas was significantly reduced in ventral, dorsal and lateral lobes of the prostate, correlating with decreased expression of SV40 Tag oncoprotein as well as inhibition of DNA synthesis and proliferation of epithelial cells in neoplastic lesions of the ventral prostate. Microarray analysis further showed leuprorelin acetate to significantly inhibit testicular steroidogenesis, suppressing the expression of SV40 Tag oncoprotein and altering the expression of a large number of genes which might be involved in the inhibition of prostate cancer progression in this rat model. (Cancer Sci 2006; 97: 459–467)