Epidermal growth factor-mediated apoptosis of MDA-MB-468 human breast cancer cells.
MDA-MB-468 human breast cancer cells lack estrogen receptors, overexpress epidermal growth factor (EGF) receptors, and are growth inhibited by EGF. We show that treatment of MDA-MB-468 cells with EGF leads to inhibition of cell proliferation, fragmentation of DNA into nucleosomal oligomers, and the development of apoptotic morphology. This treatment is associated with increased expression of c-myc, c-fos, jun family members, and transforming growth factor beta 1 mRNA and with partial proteolytic cleavage of poly(ADP-ribose) polymerase and lamin B. The observation that EGF can mediate apoptosis in EGF receptor-overexpressing cells has important implications for clinical efforts directed at the EGF receptor.
Armstrong
D K
DK
Johns Hopkins Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287.
Kaufmann
S H
SH
Ottaviano
Y L
YL
Furuya
Y
Y
Buckley
J A
JA
Isaacs
J T
JT
Davidson
N E
NE
D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D017781:Genes, Immediate-Early / Q000187:drug effects; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D004815:Epidermal Growth Factor; D011065:Poly(ADP-ribose) Polymerases