CRIPTO-1: a novel target for therapeutic intervention in human carcinoma
| Autor: | Nicola, Normanno, Antonella, De Luca, Monica R, Maiello, Caterina, Bianco, Mario, Mancino, Luigi, Strizzi, Claudio, Arra, Fortunato, Ciardiello, Sudhir, Agrawal, David S, Salomon |
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| Rok vydání: | 2004 |
| Předmět: |
EGF Family of Proteins
Membrane Glycoproteins Epidermal Growth Factor Oligonucleotides Antisense Transforming Growth Factor alpha GPI-Linked Proteins Amphiregulin Neoplasm Proteins Mice Cell Line Tumor Neoplasms Animals Humans Intercellular Signaling Peptides and Proteins RNA Messenger Glycoproteins |
| Zdroj: | International journal of oncology. 25(4) |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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