Involvement of RNA helicases p68 and p72 in colon cancer.
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 polyp-->adenoma-->adenocarcinoma transition in the colon. Furthermore, p68 and p72 form complexes with beta-catenin and promote the ability of beta-catenin to activate gene transcription. Conversely, simultaneous knockdown of p68 and p72 leads to reduced expression of the beta-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.
Shin
Sook
S
Department of Biochemistry, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Rossow
Kari L
KL
Grande
Joseph P
JP
Janknecht
Ralf
R
D000818:Animals; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051176:beta Catenin; C102004:DDX17 protein, human; D053487:DEAD-box RNA Helicases