P53 mutation alters the effect of the esophageal tumor suppressor KLF5 on keratinocyte proliferation.

ABSTRACT: Krüppel-like factor 5 (KLF5) is a key transcriptional regulator that is typically pro-proliferative in non-transformed epithelial cells but inhibits proliferation in transformed epithelial cells. However, the underlying mechanisms for this context-dependent function are not known. KLF5 is epigenetically silenced and exhibits a tumor suppressive function in esophageal squamous cell cancer (ESCC). Since p53 mutation is the most common genetic alteration in ESCC, as in other human epithelial cancers, we hypothesized that the context-dependent functions of KLF5 in cell proliferation were dependent on p53 status. In fact, in non-transformed human primary esophageal keratinocytes, when p53 was wild-type, KLF5 was pro-proliferative; however, KLF5 became anti-proliferative when p53 was mutated. KL

SUBMITTER: Yang Y 

PROVIDER: S-EPMC3507498 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature