CDK4 and pituitary gland adenoma: When p27Kip1 is deleted, or CDK4 responsiveness to INK4 inhibition is disrupted by a mutant CDK4, the effects of Hmga2 overexpression are more severe: in models of pituitary adenomas, mice develop tumors much earlier, with a higher proliferative rate and a much higher number of mitoses (as measured by Ki67 detection) [184].