Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2

被引：95

作者：

Lee, Jae Ho

Jung, Cornelia ^{[3
]}

Javadian-Elyaderani, Parisa

Schweyer, Stefan ^{[4
]}

Schuette, Dorothea ^{[3
]}

Shoukier, Moneef ^{[3
]}

Karimi-Busheri, Feridoun ^{[5
,6
]}

Weinfeld, Michael ^{[5
]}

Rasouli-Nia, Aghdass ^{[5
]}

Hengstler, Jan G. ^{[7
]}

Mantilla, Alejandra ^{[2
]}

Soleimanpour-Lichaei, Hamid Reza

Engel, Wolfgang ^{[3
]}

Robson, Craig N. ^{[2
]}

Nayernia, Karim ^{[1
]}

机构：

[1] Newcastle Univ, Int Ctr Life, Inst Human Genet, NE England Stem Cell Inst, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[2] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[3] Univ Gottingen, Inst Human Genet, D-3400 Gottingen, Germany

[4] Univ Gottingen, Dept Pathol, D-3400 Gottingen, Germany

[5] Univ Alberta, Cross Canc Inst, Dept Expt Oncol, Edmonton, AB, Canada

[6] NovaRx Corp, Stem Cell Program, San Diego, CA USA

[7] TU Dortmund IfADo, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

基金：

英国生物技术与生命科学研究理事会;

关键词：

IN-VITRO PROPAGATION; HIWI GENE; EXPRESSION; DIFFERENTIATION; MAINTENANCE; TRANSITIONS; ACTIVATION; SIGNATURE; APOPTOSIS; FAMILY;

D O I：

10.1158/0008-5472.CAN-09-2670

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer stem cell studies may improve understanding of tumor pathophysiology and identify more effective strategies for cancer treatment. In a variety of organisms, Piwil2 has been implicated in multiple roles including stem cell self-renewal, RNA silencing, and translational control. In this study, we documented specific expression of the stem cell protein Piwil2 in breast cancer with predominant expression in breast cancer stem cells. In patients who were evaluated, we determined that 90% of invasive carcinomas and 81% of carcinomas in situ exhibited highest expression of Piwil2. In breast cancer cells, Piwil2 silencing suppressed the expression of signal transducer and activator of transcription 3, a pivotal regulator of Bcl-X(L) and cyclin D1, whose downregulation paralleled a reduction in cell proliferation and survival. Our findings define Piwil2 and its effector signaling pathways as key factors in the proliferation and survival of breast cancer stem cells. Cancer Res; 70(11); 4569-79. (c) 2010 AACR.

引用

页码：4569 / 4579

页数：11

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