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Involvement of RNA Helicases p68 and p72 in Colon Cancer

Departments of ¹ Biochemistry and Molecular Biology and ² Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota

Requests for reprints: Ralf Janknecht, Mayo Clinic, Guggenheim Building 1501A, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-266-4393; E-mail: janknecht.ralf{at}mayo.edu.

The homologous proteins p68 and p72 are members of the DEAD box family of RNA helicases. Here, we show that expression of both of these helicases strongly increases during the polypadenomaadenocarcinoma transition in the colon. Furthermore, p68 and p72 form complexes with ß-catenin and promote the ability of ß-catenin to activate gene transcription. Conversely, simultaneous knockdown of p68 and p72 leads to reduced expression of the ß-catenin–regulated genes, c-Myc, cyclin D1, c-jun, and fra-1, all of which are proto-oncogenes. Moreover, transcription of the cell cycle inhibitor p21^WAF1/CIP1, whose expression is suppressed by c-Myc, is enhanced on p68/p72 knockdown. Thus, p68/p72 may contribute to colon cancer formation by directly up-regulating proto-oncogenes and indirectly by down-regulating the growth suppressor p21^WAF1/CIP1. Accordingly, knockdown of p68 and p72 in colon cancer cells inhibits their proliferation and diminishes their ability to form tumors in vivo. Altogether, these results suggest that p68/p72 overexpression is not only a potential marker of colon cancer but is also causally linked to this disease. Therefore, p68 and p72 may be novel targets in the combat against colon cancer. [Cancer Res 2007;67(16):7572–8]

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