Pathways of Proliferation and Antiapoptosis Driven in Breast Cancer Stem Cells by Stem Cell Protein Piwil2
By: Lee JH, Jung C, Javadian-Elyaderani P, Schweyer S, Schütte D, Shoukier M, Karimi-Busheri F, Weinfeld M, Rasouli-Nia A, Hengstler JG, Mantilla A, Soleimanpour-Lichaei HR, Engel W, Robson CN, Nayernia K.

Authors' Affiliations: North East England Stem Cell Institute, Institute of Human Genetics, and Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Institute of Human Genetics and Department of Pathology, Georg-August University of Göttingen, Göttingen, Germany; Department of Experimental Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada; NovaRx Corporation, Stem Cell Program, San Diego, California; and Leibniz Research Centre for Working Environment and Human Factors at the TU-Dortmund (IfADo), Dortmund, Germany.
Cancer Res. 2010 May 11.

Abstract

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); OF1-11. (c)2010 AACR.

PMID: 20460541 [PubMed - as supplied by publisher] Source: National Library of Medicine.






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