Cripto-1 induces apoptosis in HC-11 mouse mammary epithelial cells

M. L. De Santis, I. Martinez-Lacaci, C. Bianco, M. Seno, B. Wallace-Jones, N. Kim, A. Ebert, C. Wechselberger, D. S. Salomon

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Cripto-1 (CR-1) is an epidermal growth factor (EGF)-related protein. CR-1 can inhibit β-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 β-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 p27(kip1) and p21Bax did not change after exposure to CR-1 for 18 h, the levels of Bcl-x(L) 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.

Original languageEnglish
Pages (from-to)189-196
Number of pages8
JournalCell Death and Differentiation
Issue number2
Publication statusPublished - Feb 2000


  • Apoptosis
  • Caspase activation
  • Cripto-1
  • Mammary epithelial cells

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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