Abstract
B lymphoma Mo-MLV insertion region 1 (Bmi-1) is highly expressed in a variety of cancers and has been shown to regulate cell proliferation. The INK4a/ARF tumor suppressor gene locus is one of the major targets of Bmi-1. In the present study, we chose two lung adenocarcinoma cell lines, A549 cells (without INK4a locus) and SPC-A1 cells (with INK4a locus), to investigate if the small hairpin RNA-mediated knockdown of Bmi-1 could inhibit the proliferation of lung adenocarcinoma cells, and to delineate the possible mechanism underlying Bmi-1 modulation of cell proliferation. We also investigated the potential pathway underlying Bmi-1 regulation of lung adenocarcinoma cell proliferation in different genetic backgrounds. To this end, we used shRNA to knockdown Bmi-1 expression in lung adenocarcinoma cells, which led to inhibition of cell growth, colony formation in vitro, and tumorigenesis in vivo. In addition, phosphorylated Akt and cyclin D1 expression were downregulated, p21 and p27 levels were upregulated, and p16 expression remained unchanged in SPC-A1 cells. These data indicate that Bmi-1 might modulate the growth of lung adenocarcinoma cells in an INK4a-p16 independent pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma of Lung
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Animals
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Cell Line, Tumor
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Cell Proliferation
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Cyclin D1 / antagonists & inhibitors
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Cyclin D1 / genetics*
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Cyclin D1 / metabolism
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / agonists
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Cyclin-Dependent Kinase Inhibitor p27 / genetics*
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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G1 Phase Cell Cycle Checkpoints / genetics
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Gene Expression Regulation, Neoplastic*
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Genetic Loci
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Humans
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Lung Neoplasms / genetics*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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Mice
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Mice, Nude
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Organ Specificity
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Polycomb Repressive Complex 1 / antagonists & inhibitors
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Polycomb Repressive Complex 1 / genetics*
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Polycomb Repressive Complex 1 / metabolism
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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RNA, Small Interfering / genetics*
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RNA, Small Interfering / metabolism
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Signal Transduction
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p21-Activated Kinases / genetics*
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p21-Activated Kinases / metabolism
Substances
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Bmi1 protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Cyclin D1
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Cyclin-Dependent Kinase Inhibitor p27
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Polycomb Repressive Complex 1
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p21-Activated Kinases