title: Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit the colonization of premalignant human breast cells overexpressing cyclin D1.
abstract: The role of cyclin D1 overexpression in human breast premalignancy was investigated using immortal, nontumorigenic MCF-10A cells. Previous work documented that cyclin D1 overexpression promoted in vitro anchorage-independent colonization. We now report that the colonization of MCF-10A cyclin D1 transfectants was preferentially inhibited by gamma-radiation and specific classes of apoptosis inducers [Apo-2 ligand (Apo-2L), but not tumor necrosis factor alpha]. Antibody inhibition studies and semiquantitative PCR indicated that radiation inhibition of colonization was partially mediated via the Apo2L/TRAIL pathway. The apoptotic removal of cyclin D1-overexpressing, colonization-competent premalignant breast cells by Apo2L/TRAIL or other biologicals may represent a novel approach to the prevention of breast cancer.
authors.affiliation: Women's Cancers Section, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Fukushima
authors.forename: W
authors.initials: W
authors.lastname: DeGraff
authors.forename: J B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Stetler Stevenson
authors.forename: A
authors.initials: A
authors.lastname: Ashkenazi
authors.forename: P S
authors.initials: PS
authors.lastname: Steeg
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000532:radiotherapy; D002455:Cell Division / Q000528:radiation effects; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D019938:Cyclin D1