The loss of TGF-β signaling promotes prostate cancer metastasis

被引:84
作者
Tu, WH [1 ]
Thomas, TZ
Masumori, N
Bhowmick, NA
Gorska, AE
Shyr, Y
Kasper, S
Case, T
Roberts, RL
Shappell, SB
Moses, HL
Matusik, RJ
机构
[1] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Med Ctr N A1302, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Vanderbilt Prostate Canc Ctr, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA
[6] Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan
来源
NEOPLASIA | 2003年 / 5卷 / 03期
关键词
transforming growth factor-beta; prostate cancer; metastasis; probasin; transgenic mice;
D O I
10.1016/S1476-5586(03)80058-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In breast and colon cancers, transforming growth factor (TGF)-beta signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGF-beta type II receptor (TbetaRII) with higher tumor grade. To determine the effect of an inhibited TGF-beta pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative TbetaRII mutant (DNIIR) in the prostate. Transgene(s) and TGF-beta1 expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGF-beta signaling, correlated with expression of the DNIIR. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGF-beta signaling in prostate cancer plays a causal role in promoting tumor metastasis.
引用
收藏
页码:267 / 277
页数:11
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