Abnormal prostate development in C3(1)-bcl-2 transgenic mice

• Published in: The Prostate Vol. 32; no. 1; pp. 16 - 26
• Main Authors: Zhang, Xuejun, Chen, Min-Wei, Ng, Albert, Ng, Po-Ying, Lee, Chung, Rubin, Mark, Olsson, Carl A., Buttyan, Ralph
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15.06.1997; Wiley-Liss
• Subjects: Animals; Apoptosis; Autoradiography; bcl-2; Biological and medical sciences; Blotting, Southern; Blotting, Western; Disease Models, Animal; DNA Primers; DNA, Complementary; Female; Gene Expression Regulation; Humans; Male; Medical sciences; Mice; Mice, Inbred Strains; Mice, Transgenic; Nephrology. Urinary tract diseases; Ovary - chemistry; Polymerase Chain Reaction; Prostate - embryology; Prostate - metabolism; Prostate - pathology; prostate gland; prostate-steroid-binding protein; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - genetics; Testis - chemistry; transgenic mice; Tumors of the urinary system; Urinary tract. Prostate gland; Animal model; Urinary system disease; Prostate disease; Pathogenesis; Rodentia; Transgenic animal; Cell biology; Male; Gene expression; Carcinogenesis; Polymerase chain reaction; Vertebrata; Mammalia; Mouse; Male genital diseases; Prostate; Apoptosis
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/(SICI)1097-0045(19970615)32:1<16::AID-PROS3>3.0.CO;2-A

BACKGROUND Recent hypotheses to explain the etiology of abnormal growth associated with prostate disease have invoked perturbations in the rate of apoptosis as an important contributor to the onset and progression of these diseases. For this reason, the apoptosis suppressing oncoprotein bcl‐2 has come under scrutiny with regards to its role in prostate diseases. In order to evaluate the role of bcl‐2 in human prostate disease and to develop an animal model to test anti‐bcl‐2 therapies, we generated transgenic mice in which bcl‐2 expression is targeted to the mouse prostate gland. METHODS Mouse embryos were microinjected with recombinant DNA constructed by fusing a modified rat C3(1) promotor element to cDNA encoding human bcl‐2. Presence of the C3(1)‐bcl‐2 transgene in progeny was identified by Southern blot and polymerase chain reaction (PCR) analysis. RNase protection assays were used to analyze RNA from 15 organs of these mice. Western blot assays and immunohistochemical staining were used to confirm the tissue‐specific protein expression of human bcl‐2 and its cellular localization. RESULTS Three lines of C3(1)‐bcl‐2 transgenic mice were established. Founder mice carried 2–20 copies of the transgene. Expression of human bcl‐2 from the transgene was limited to the prostate gland and testis of males as well as the uterus of females. In the prostate gland, human bcl‐2 protein was found only in prostatic epithelial cells. Microscopic analysis of prostate glands from individual males (three lines) showed that these glands were often abnormal, with increased accumulation of cells in the prostatic stroma as well as the epithelium. CONCLUSIONS These transgenic mice appear to provide a novel animal model for studying neoplastic development of the prostate, with particular emphasis on the bcl‐2 protein and the role of apoptosis regulation in such development. Prostate 32:16–26, 1997. © 1997 Wiley‐Liss, Inc.