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Toxicol Pathol. 2015 Feb;43(2):186-97. doi: 10.1177/0192623314531351. Epub 2014 Apr 17.

Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

Author information

1
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA Present address: Department of Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA lisa.berman-booty@jefferson.edu.
2
Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
3
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA Comparative Pathology and Mouse Phenotyping Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
4
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.
5
Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
6
Division of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan, China.

Abstract

Male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice are frequently used in prostate cancer research because their prostates consistently develop a series of preneoplastic and neoplastic lesions. Disease progression in TRAMP mouse prostates culminates in metastatic, poorly differentiated carcinomas with neuroendocrine features. The androgen dependence of the rat probasin promoter largely limits transgene expression to the prostatic epithelium. However, extra-prostatic transgene-positive lesions have been described in TRAMP mice, including renal tubuloacinar carcinomas, neuroendocrine carcinomas of the urethra, and phyllodes-like tumors of the seminal vesicle. Here, we describe the histologic and immunohistochemical features of 2 novel extra-prostatic lesions in TRAMP mice: primary anaplastic tumors of uncertain cell origin in the midbrain and poorly differentiated adenocarcinomas of the submandibular salivary gland. These newly characterized tumors apparently result from transgene expression in extra-prostatic locations rather than representing metastatic prostate neoplasms because lesions were identified in both male and female mice and in male TRAMP mice without histologically apparent prostate tumors. In this article, we also calculate the incidences of the urethral carcinomas and renal tubuloacinar carcinomas, further elucidate the biological behavior of the urethral carcinomas, and demonstrate the critical importance of complete necropsies even when evaluating presumably well characterized phenotypes in genetically engineered mice.

KEYWORDS:

TRAMP mouse; extra-prostatic neoplasms; probasin promoter

PMID:
24742627
PMCID:
PMC4201646
DOI:
10.1177/0192623314531351
[Indexed for MEDLINE]
Free PMC Article

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