title: 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 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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL, USA.
authors.forename: Aruna S
authors.initials: AS
authors.lastname: Jaiswal
authors.forename: Harekrushna
authors.initials: H
authors.lastname: Panda
authors.forename: Christine A
authors.initials: CA
authors.lastname: Pampo
authors.forename: Dietmar W
authors.initials: DW
authors.lastname: Siemann
authors.forename: C Gary
authors.initials: CG
authors.lastname: Gairola
authors.forename: Robert
authors.initials: R
authors.lastname: Hromas
authors.forename: Satya
authors.initials: S
authors.lastname: Narayan
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001080:Apurinic Acid / Q000235:genetics; D001564:Benzo(a)pyrene / Q000633:toxicity; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics; D012906:Smoke / Q000009:adverse effects; D014026:Nicotiana / Q000737:chemistry
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D002273:Carcinogens; D034741:RNA, Small Interfering; D012906:Smoke; D001080:Apurinic Acid; D001564:Benzo(a)pyrene
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