期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 118, 期 9, 页码 3051-3064出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI34764
关键词
-
资金
- National Cancer Institute (NCI) [U01-CA84294, R01-CA115717, SPORE CA92629]
- T.J. Martell Foundation
- Sands Family Foundation
- Ruth L. Kirschstein National Research Service Award [1F31CA110625-01]
- Swiss National Science Foundation [81BS-69441]
- Swiss Urologic Association
The AKT/mammalian target of rapamycin (AKT/mTOR) and ERK MAPK signaling pathways have been shown to cooperate in prostate cancer progression and the transition to androgen-independent disease. We have now tested the effects of combinatorial inhibition of these pathways on prostate tumorigenicity by performing preclinical studies using a genetically engineered mouse model of prostate cancer. We report here that combination therapy using rapamycin, an inhibitor of mTOR, and PD0325901, an inhibitor of MAPK kinase 1 (MEK; the kinase directly upstream of ERK), inhibited cell growth in cultured prostate cancer cell fines and tumor growth particularly for androgen-independent prostate tumors in the mouse model. We further showed that such inhibition leads to inhibition of proliferation and upregulated expression of the apoptotic regulator Bcl-2-interacting mediator of cell death (Bim). Furthermore, analyses of human prostate cancer tissue microarrays demonstrated that AKT/mTOR and ERK MAPK signaling pathways are often coordinately deregulated during prostate cancer progression in humans. We therefore propose that combination therapy targeting AKT/mTOR and ERK MAPK signaling pathways may be an effective treatment for patients with advanced prostate cancer, in particular those with hormone-refractory disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据