CRIPTO-1: a novel target for therapeutic intervention in human carcinoma.

Nicola Normanno*, Antonella De Luca, Monica R. Maiello, Caterina Bianco, Mario Mancino, Luigi Strizzi, Claudio Arra, Fortunato Ciardiello, Sudhir Agrawal, David S. Salomon

*Corresponding author for this work

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Evidence suggests that CRIPTO-1 (CR-1) might be involved in the pathogenesis of human carcinoma. In the present study, we have screened the expression of CR-1 mRNA and protein in a wide panel of human cancer cell lines by using reverse transcriptase (RT)-PCR, real-time PCR and immunocytochemistry. Results of these experiments demonstrate that CR-1 is expressed in several, different carcinoma types. The anchorage-independent growth of colon, ovarian, lung and breast carcinoma cells was significantly inhibited by treatment with anti-CR-1 second generation antisense oligonucleotides. Similar results were obtained with anti-transforming growth factor alpha (TGF-alpha) and anti-amphiregulin (AR) antisense oligonucleotides. Treatment of carcinoma cells with CR-1 antisense oligonucleotides resulted in a significant reduction in the levels of expression of CR-1 mRNA and protein, and in the levels of activation of Akt. Finally, oral administration of either CR-1, AR or TGF-alpha antisense oligonucleotides produced a significant reduction in the growth of GEO colon carcinoma xenografts in nude mice that was associated with a reduction in the levels of expression of the target proteins. Taken together, these data strongly suggest that CR-1 might represent a novel target for therapeutic intervention in different carcinoma types.

Original languageEnglish (US)
Pages (from-to)1013-1020
Number of pages8
JournalInternational Journal of Oncology
Volume25
Issue number4
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Normanno, N., De Luca, A., Maiello, M. R., Bianco, C., Mancino, M., Strizzi, L., Arra, C., Ciardiello, F., Agrawal, S., & Salomon, D. S. (2004). CRIPTO-1: a novel target for therapeutic intervention in human carcinoma. International Journal of Oncology, 25(4), 1013-1020.