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Selenoprotein deficiency increases prostate carcinogenesis in a transgenic mouse model
Author(s) -
DiwadkarNavsariwala Veda,
Prins Gail S.,
Swanson Steven M.,
Diamond Alan M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a428-c
Subject(s) - selenoprotein , prostate cancer , carcinogenesis , intraepithelial neoplasia , genetically modified mouse , prostate , transgene , biology , cancer research , selenoprotein p , tramp , prostatic diseases , cancer , medicine , endocrinology , glutathione peroxidase , genetics , gene , oxidative stress , superoxide dismutase
Considerable animal and human data point towards a chemopreventive role for selenium, however its mechanism of action remains unclear. Selenoproteins are likely involved in the anti‐carcinogenic effects of selenium wherein genetic polymorphism data and antioxidant functions provide support for this role. In order to investigate the function of selenoproteins in prostate carcinogenesis in the absence of a variation in selenium intake, a transgenic mouse model was developed. These mice, referred to as i 6 A − /Tag expressed reduced levels of selenoproteins due to the presence of a mutant selenocysteine tRNA, and an increased risk for prostate cancer due to the directed expression of the SV40 large T and small t oncogenes in the prostate. The i 6 A − /Tag mice were compared to control WT/Tag for the presence, degree and progression of prostatic intraepithelial neoplasia (PIN). A clear difference in prostate histopathology was observed, with the selenoprotein deficient mice displaying an increased predisposition towards higher‐grade lesions with time. In the early weeks significantly more prostates were normal in the WT/Tag compared to the i 6 A − /Tag mice, however as time elapsed a greater shift from low‐grade to high‐grade PIN was apparent in the selenoprotein deficient mice indicative of an accelerated development towards prostate cancer. These data implicate selenoprotein levels in prostate cancer progression. This work was supported by grants from NIH # 5 RO1 CA101053‐02 and DOD # W18XWH‐05‐1‐0009.