Adenomatous Polyposis Coli-Mediated Accumulation of Abasic DNA Lesions Lead to Cigarette Smoke Condensate-Induced Neoplastic Transformation of Normal Breast Epithelial Cells

Abstract Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it int...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) N.Y.), 2013-04, Vol.15 (4), p.454-460
Main Authors: Jaiswal, Aruna S, Panda, Harekrushna, Pampo, Christine A, Siemann, Dietmar W, Gairola, C. Gary, Hromas, Robert, Narayan, Satya
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli Protein - genetics
Adenomatous Polyposis Coli Protein - metabolism
Anaphase-promoting complex
Animals
Apurinic Acid - genetics
Benzo(a)pyrene - toxicity
Breast - pathology
Breast Neoplasms - etiology
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Carcinogens - toxicity
Cell Line
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
DNA Damage
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Female
Gene Expression
Gene Knockdown Techniques
Humans
Mice
Mice, Nude
Neoplasm Transplantation
Nicotiana - chemistry
Oncology
RNA, Small Interfering - genetics
Smoke - adverse effects
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Summary:Abstract Adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation, and apoptosis. Recently, we found a new role of APC in base excision repair (BER) and showed that it interacts with DNA polymerase β and 5′-flap endonuclease 1 and interferes in BER. Previously, we have also reported that cigarette smoke condensate (CSC) increases expression of APC and enhances the growth of normal human breast epithelial (MCF10A) cells in vitro . In the present study, using APC overexpression and knockdown systems, we have examined the molecular mechanisms by which CSC and its major component, Benzo[ α ]pyrene, enhances APC-mediated accumulation of abasic DNA lesions, which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic transformation of MCF10A cells in an orthotopic xenograft model.
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1593/neo.13176