Radiation and the Apo2L/TRAIL apoptotic pathway preferentially inhibit the colonization of premalignant human breast cells overexpressing cyclin D1.
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.
Zhou
Q
Q
Women's Cancers Section, Division of Clinical Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA.
Fukushima
P
P
DeGraff
W
W
Mitchell
J B
JB
Stetler Stevenson
M
M
Ashkenazi
A
A
Steeg
P S
PS
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*
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