Defective Myb function ablates Cyclin E1 expression and perturbs intestinal carcinogenesis

Abstract

Cyclin E1 is essential for the reentry of quiescent cells into the cell cycle. When hypomorphic mutant Myb mice (MybPlt4) were examined, it was noted that Cyclin E1 (Ccne1) expression was reduced. Furthermore, the induction of Ccne1 in recovering intestinal epithelia following radiation-induced damage was ablated in Myb-mutant mice. These data prompted us to investigate whether Myb directly regulated Ccne1 and to examine whether elevated Myb in colorectal cancer is responsible for Cyclin E1-driven tumor growth. Here, it was found that Myb/MYB and Ccne1/CCNE1 expressions were coupled in both mouse and human adenomas. In addition, the low molecular weight Cyclin E1 was the predominant form in ..