Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by leuprorelin, a luteinizing hormone-releasing hormone agonist.
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.
Said
Mahmoud M
MM
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan.
Hokaiwado
Naomi
N
Tang
Mingxi
M
Ogawa
Kumiko
K
Suzuki
Shugo
S
Ghanem
Hala M
HM
Esmat
Amr Y
AY
Asamoto
Makoto
M
Refaie
Fawzia M
FM
Shirai
Tomoyuki
T
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
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