title: Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone-releasing hormone agonist.
abstract: 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.
authors.affiliation: Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Said
authors.forename: Naomi
authors.initials: N
authors.lastname: Hokaiwado
authors.forename: Mingxi
authors.initials: M
authors.lastname: Tang
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shugo
authors.initials: S
authors.lastname: Suzuki
authors.forename: Hala M
authors.initials: HM
authors.lastname: Ghanem
authors.forename: Amr Y
authors.initials: AY
authors.lastname: Esmat
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Fawzia M
authors.initials: FM
authors.lastname: Refaie
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000727:Androgen-Binding Protein / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D007150:Immunohistochemistry; D016729:Leuprolide / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000187:drug effects; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012669:Seminal Vesicles / Q000187:drug effects; D013739:Testosterone / Q000097:blood
chemical_list: D000727:Androgen-Binding Protein; D000952:Antigens, Polyomavirus Transforming; D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D011944:Receptors, Androgen; C027519:probasin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide