Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence.
Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence.
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DOI：
10.1038/onc.2010.197
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发表时间：
2010-07-29
期刊：
影响因子：
8
通讯作者：
Tang, D. G.
中科院分区：
文献类型：
--
作者：
Suraneni, M. V.;Schneider-Broussard, R.;Moore, J. R.;Davis, T. C.;Maldonado, C. J.;Li, H.;Newman, R. A.;Kusewitt, D.;Hu, J.;Yang, P.;Tang, D. G.
15-Lipoxygenase 2 (15-LOX2), a lipid-peroxidizing enzyme, is mainly expressed in the luminal compartment of the normal human prostate and often decreased or lost in prostate cancer. Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we established prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, transgenic expression of 15-LOX2 or 15-LOX2sv-b, a splice variant that lacks the arachidonic acid metabolizing activity, resulted in age-dependent prostatic hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in luminal and Ki-67+ cells; however, 15-LOX2-transgenic prostates also showed a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2, but not 15-LOX2sv-b, transgenic prostate showed upregulation of several well-known stem/progenitor cell molecules including Sca-1, Trop2, p63, Nkx3.1 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to prostatic intraprostate neoplasia (PIN) or carcinoma and, mechanistically, prostate lobes (especially those of the 15-LOX2 mice) showed a dramatic increase in senescent cells as revealed by increased SA-βgal, p27Kip1 and HP1γ staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia and also induces cell senescence, which may, in turn, function as a barrier to tumor development.
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DOI：
10.1046/j.1432-1327.1999.00818.x
发表时间：
1999-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
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作者：
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影响因子：
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DOI：
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发表时间：
2006-04-01
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3
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DOI：
10.1158/1541-7786.mcr-08-0137
发表时间：
2009-03
期刊：
Molecular cancer research : MCR
影响因子：
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作者：
Ibaragi S;Yoshioka N;Kishikawa H;Hu JK;Sadow PM;Li M;Hu GF
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Hu GF
影响因子：
8
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