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Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo

文献类型：期刊论文

作者Chen, Yi6,7; Alvarez, Edwin A.7; Azzam, Diana1,7; Wander, Seth A.5,7; Guggisberg, Natalia7; Jorda, Merce3,7; Ju, Zhenlin2; Hennessy, Bryan T.2; Slingerland, Joyce M.1,4,7
刊名BREAST CANCER RESEARCH AND TREATMENT
出版日期2011-07
卷号128期号:1页码:69-78
关键词Fulvestrant Tamoxifen Src inhibitor Cell cycle p27 Breast cancer
ISSN号0167-6806
DOI10.1007/s10549-010-1024-7
文献子类Article
英文摘要Antiestrogen therapies arrest susceptible estrogen receptor (ER)-positive breast cancers by increasing p27. Since Src phosphorylates p27 to promote p27 proteolysis, Src activation observed in up to 40% of ER-positive cancers may contribute to antiestrogen resistance. In this article, we show that treatment with the Src-inhibitor saracatinib (AZD0530) together with ER-blocking drugs increased breast cancer cell cycle arrest via p27. Saracatinib and fulvestrant together more effectively increased p27, reduced Ki67, and impaired MDA-MB-361 xenograft tumor growth in vivo than either of the drugs alone. In contrast, saracatinib monotherapy rapidly gave rise to drug resistance. Since combined ER and Src inhibition delays development of resistance in vivo, these data support further clinical investigation of saracatinib in combination with fulvestrant for women with ER-positive breast cancer. Proteomic analysis revealed striking bypass activation of the mTOR pathway in saracatinib-resistant tumors. mTORC1 activation also arose following long-term culture of ER-positive breast cancer lines in the presence of saracatinib. These data indicate the utility of proteomic analysis of drug-resistant tumors to identify potential means of drug resistance. The use of mTOR kinase inhibitors with saracatinib may subvert drug resistance and prove to be more effective than saracatinib alone.
WOS关键词RETINOBLASTOMA PROTEIN-PHOSPHORYLATION ; CELL-CYCLE ; ESTROGEN-RECEPTOR ; AROMATASE INHIBITORS ; POSTMENOPAUSAL WOMEN ; DOUBLE-BLIND ; MCF-7 CELLS ; C-SRC ; TAMOXIFEN ; ACTIVATION
资助项目Flight Attendant Medical Research Institute[00000000] ; Breast Cancer Research Foundation[00000000] ; Avon-AACR Fellowship[00000000] ; Doris Duke Charitable Foundation[00000000]
WOS研究方向Oncology
语种英语
WOS记录号WOS:000291656200008
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/278486]  
专题药理学第一研究室
通讯作者Chen, Yi
作者单位1.Univ Miami, Miller Sch Med, Dept Biochem & Mol Biol, Miami, FL 33136 USA;
2.Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA;
3.Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA;
4.Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA
5.Univ Miami, Miller Sch Med, Canc Biol Grad Program, Miami, FL 33136 USA;
6.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China;
7.Univ Miami, Braman Family Breast Canc Inst, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA;
推荐引用方式
GB/T 7714		 Chen, Yi,Alvarez, Edwin A.,Azzam, Diana,et al. Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo[J]. BREAST CANCER RESEARCH AND TREATMENT,2011,128(1):69-78.
APA Chen, Yi.,Alvarez, Edwin A..,Azzam, Diana.,Wander, Seth A..,Guggisberg, Natalia.,...&Slingerland, Joyce M..(2011).Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo.BREAST CANCER RESEARCH AND TREATMENT,128(1),69-78.
MLA Chen, Yi,et al."Combined Src and ER blockade impairs human breast cancer proliferation in vitro and in vivo".BREAST CANCER RESEARCH AND TREATMENT 128.1(2011):69-78.

入库方式： OAI收割

来源：上海药物研究所

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