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

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.

• Authors: Nicola Normanno, Antonella De Luca, Monica R Maiello, Caterina Bianco, Mario Mancino, Luigi Strizzi, Claudio Arra, Fortunato Ciardiello, Sudhir Agrawal, David S Salomon
• Journal: International journal of oncology (Int J Oncol) Vol. 25 Issue 4 Pg. 1013-20 (Oct 2004) ISSN: 1019-6439 [Print] Greece
• PMID: 15375551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AREG protein, human
• Amphiregulin
• Areg protein, mouse
• EGF Family of Proteins
• GPI-Linked Proteins
• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Membrane Glycoproteins
• Neoplasm Proteins
• Oligonucleotides, Antisense
• RNA, Messenger
• TDGF1 protein, human
• Transforming Growth Factor alpha
• Epidermal Growth Factor

Topics

• Amphiregulin
• Animals
• Cell Line, Tumor
• EGF Family of Proteins
• Epidermal Growth Factor (antagonists & inhibitors, genetics)
• GPI-Linked Proteins
• Glycoproteins (antagonists & inhibitors)
• Humans
• Intercellular Signaling Peptides and Proteins
• Membrane Glycoproteins (antagonists & inhibitors, genetics)
• Mice
• Neoplasm Proteins (antagonists & inhibitors, genetics)
• Neoplasms (therapy)
• Oligonucleotides, Antisense (pharmacology, therapeutic use)
• RNA, Messenger (analysis)
• Transforming Growth Factor alpha (antagonists & inhibitors)