Consistent with these findings, the second-generation CDK1 and CDK2 inhibitor R-roscovitine (seliciclib), inhibiting the association of CDK2/cyclin E complexes (28), caused a reduction of POMC promoter expression in ~40% in a double transgenic POMC : PTTG zebrafish model, and in murine AtT20 corticotroph adenoma models (29–31) Other studies also found murine p27 knock-out was associated with enlarging corticotroph tumors within 12 months (32–34), and molecular research of recurrent human corticotroph adenomas or carcinomas showed lower or absent p27 staining (35). This evidence concerns the gene PTTG1 and ACTH-producing pituitary gland adenoma.