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Normanno, N. et al.

Normanno, De Luca, Maiello, Bianco, Mancino, Strizzi, Arra, Ciardiello, Agrawal, Salomon,

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

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.[1]

References

CRIPTO-1: a novel target for therapeutic intervention in human carcinoma. Normanno, N., De Luca, A., Maiello, M.R., Bianco, C., Mancino, M., Strizzi, L., Arra, C., Ciardiello, F., Agrawal, S., Salomon, D.S. Int. J. Oncol. (2004) [Pubmed]

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