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BMI1 as a novel target for drug discovery in cancer
Author(s) -
Cao Liangxian,
Bombard Jenelle,
Cintron Katherine,
Sheedy Josephine,
Weetall Marla L.,
Davis Thomas W.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23234
Subject(s) - bmi1 , p14arf , cancer research , biology , chromatin , gene silencing , cancer stem cell , clonogenic assay , senescence , stem cell , cancer , apoptosis , carcinogenesis , microbiology and biotechnology , genetics , tumor suppressor gene , gene
Growing evidence has demonstrated that clonogenic cancer stem (initiating) cells are responsible for tumor regrowth and disease relapse. Bmi‐1 plays a critical role in the self‐renewal of adult stem cells. The Bmi‐1 protein is elevated in many types of cancers, and experimental reduction of Bmi‐1 protein levels by small interfering RNA (siRNA) causes apoptosis and/or senescence in tumor cells in vitro and increases susceptibility to cytotoxic agents. The Bmi‐1 protein has no known enzymatic activity, but serves as the key regulatory component of the PRC1 complex (polycomb repressive complex‐1). This complex influences chromatin structure and regulates transcriptional activity of a number of important loci including the Ink4a locus which encodes the tumor suppressor proteins p16 Ink4a and p14 Arf . In this prospective study, we will discuss the implication of BMI1 in cancers, the biology of BMI1, and the regulatory control of BMI1 expression. The target validation and the future prospects of targeting BMI1 in cancer therapy are also discussed. J. Cell. Biochem. 112: 2729–2741, 2011. © 2011 Wiley‐Liss, Inc.