Targeting Cyclin D1 in Non-small Cell Lung Cancer and Mesothelioma Cells by Antisense Oligonucleotides

Cyclin D1 overexpression exists in multiple types of cancer and is a potential chemopreventive or therapeutic target. Non-small cell lung cancer and mesothelioma cells were incubated with antisense oligonucleotides (ASO) to cyclin D1 (CD1) and evaluated for effects on cellular proliferation, apoptos...

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Bibliographic Details
Published in:Anticancer research 2011-11, Vol.31 (11), p.3683-3690
Main Authors: SAINI, Shamsher S, KLEIN, Mark A
Format: Article
Language:English
Subjects:
Antisense oligonucleotides
Apoptosis
Biological and medical sciences
Blotting, Western
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Carcinoma, Non-Small-Cell Lung - therapy
Cell Cycle
Cell Cycle Proteins - metabolism
Cell Proliferation
Cyclin D1 - antagonists & inhibitors
Cyclin D1 - genetics
Humans
Immunoprecipitation
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Lung Neoplasms - therapy
Medical sciences
Mesothelioma - genetics
Mesothelioma - pathology
Mesothelioma - therapy
Oligonucleotides, Antisense - pharmacology
Phosphorylation
Pneumology
Tumor Cells, Cultured
Tumors
Tumors of the respiratory system and mediastinum
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Summary:Cyclin D1 overexpression exists in multiple types of cancer and is a potential chemopreventive or therapeutic target. Non-small cell lung cancer and mesothelioma cells were incubated with antisense oligonucleotides (ASO) to cyclin D1 (CD1) and evaluated for effects on cellular proliferation, apoptosis, expression of cell cycle-specific proteins, and protein phosphorylation states. ASO to CD1 inhibited proliferation of non-small lung cancer cells and mesothelioma cells. ASO induced apoptosis as determined by TUNEL assay. Western blot analysis of cell lysate showed that ASO inhibited the de novo synthesis of CD1, CD3, and CDK2 in multiple cell lines. Immunoprecipitation and immunoblotting with phosphoantibodies demonstrated that CD1, CD3, and CDK2 exist in a phosphorylated state. The work demonstrates that non-small cell lung cancer and mesothelioma cells respond to ASO-mediated cellular growth inhibition. These findings make ASO to CD1 attractive as a potential therapeutic for mesothelioma and non-small cell lung cancer.
ISSN:0250-7005
1791-7530