Down-regulation of HER2/neu expression induces apoptosis in human cancer cells that overexpress HER2/neu.
The HER2/neu oncogene is overexpressed in a significant fraction of human tumors; such overexpression is thought to play a role in the aberrant proliferation of cancer cells. The effects of HER2/neu-specific phosphorothioate antisense oligodeoxyribonucleotides on HER2/neu expression, tumor cell proliferation, and activation of apoptotic cell death pathways have been examined. Antisense treatment down-regulates HER2/neu expression in a dose-dependent and sequence-specific manner. HER2/neu antisense treatment specifically inhibits the growth of tumor lines that overexpress HER2/neu, but it has little effect on the growth of tumor cells that express low levels of HER2/neu. Down-regulation of HER2/neu expression is not only cytostatic, but it also results in the activation of apoptotic cell death pathways in cells that overexpress HER2/neu. These results suggest that, in addition to stimulating tumor cell proliferation, HER2/neu overexpression in cancer cells acts as an antiapoptotic cell survival factor.
Roh
H
H
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Pippin
J
J
Drebin
J A
JA
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D014407:Tumor Cells, Cultured
D053148:Caspase 3; D020169:Caspases; D016376:Oligonucleotides, Antisense; D018719:Erb-b2 Receptor Tyrosine Kinases; C505407:CASP3 protein, human