Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells.
Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit beta-casein and whey acidic protein expression in mouse mammary epithelial cells. The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bis-benzimide stained nuclei, TUNEL assay and cell death ELISA. Apoptosis could be observed after 2 days of exposure of confluent HC-11 cells to CR-1 in the absence of the survival factors EGF and insulin, with maximum apoptosis occurring at 3 days. A reduction in poly(ADP-ribose) polymerase (PARP) expression and an increase in beta-catenin cleavage was found after 18 h of exposure to CR-1 suggesting that apoptosis was preceded by the induction of a caspase activity since the caspase inhibitor ZFAD.FMK could block the CR-1-induced reduction in PARP expression and CR-1-induced apoptosis. CR-1 was found to increase the expression of caspase-3-like protease. Although, the levels of p27kip1 and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-xL became undetectable. These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-xL.
De Santis
M L
ML
Department of Molecular Pathology, Walter Reed Army Institute of Research, Washington DC 20307, USA.
Martinez-Lacaci
I
I
Bianco
C
C
Seno
M
M
Wallace-Jones
B
B
Kim
N
N
Ebert
A
A
Wechselberger
C
C
Salomon
D S
DS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D020287:In Situ Nick-End Labeling; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins; D051379:Mice; D009363:Neoplasm Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C489450:Tdgf1 protein, mouse; D004815:Epidermal Growth Factor; D020169:Caspases