SMAD4 and intestinal cancer: Furthermore, primary cultures of Villin‐Cre; Smad4F/F; Trp53F/F intestinal cancer cells (primary #1) revealed a reduction in p21 induction after etoposide treatment in comparison with Smad4‐ and/or p53‐restored cells (Figure 2I), implying the reciprocal regulation of p21 by Smad4 and p53.