Selenoprotein deficiency accelerates prostate carcinogenesis in a transgenic model.
Considerable animal and human data have indicated that selenium is effective in reducing the incidence of several different types of cancer, including that of the prostate. However, the mechanism by which selenium inhibits carcinogenesis remains unknown. One possibility is that dietary selenium influences the levels of selenium-containing proteins, or selenoproteins. Selenoproteins contain selenium in the form of selenocysteine and perform a variety of cellular functions, including antioxidant defense. To determine whether the levels of selenoproteins can influence carcinogenesis independent of selenium intake, a unique mouse model was developed by breeding two transgenic animals: mice with reduced selenoprotein levels because of the expression of an altered selenocysteine-tRNA (i6A-) and mice that develop prostate cancer because of the targeted expression of the SV40 large T and small t oncogenes to that organ [C3(1)/Tag]. The resulting bigenic animals (i6A-/Tag) and control WT/Tag mice were assessed for the presence, degree, and progression of prostatic epithelial hyperplasia and nuclear atypia. The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins.
Diwadkar-Navsariwala
Veda
V
Department of Human Nutrition, University of Illinois, Chicago, IL 60612, USA.
Prins
Gail S
GS
Swanson
Steven M
SM
Birch
Lynn A
LA
Ray
Vera H
VH
Hedayat
Samad
S
Lantvit
Daniel L
DL
Diamond
Alan M
AM
D000818:Animals; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D051140:Selenoproteins / Q000172:deficiency* / Q000235:genetics
D051140:Selenoproteins; D005979:Glutathione Peroxidase