SMAD4 and adenocarcinoma: For instance, a study on mutant cis-Apc/Smad4 mice spontaneously developing adenocarcinoma of the intestine demonstrated two-fold higher expression of Ccl9 mRNA in polyps than in wild-type C57BL/6, as well as five-fold higher expression of CCL9 protein in polyps than of Apc+/D716 mice [6].