TIP30 nuclear translocation negatively regulates EGF-dependent cyclin D1 transcription in human lung adenocarcinoma.

Aberrant epidermal growth factor (EGF)-dependent signaling plays a key role in the progression of human carcinomas. We found that TIP30, a tumor suppressor protein, translocated into the nucleus of human lung adenocarcinoma cells following EGF treatment, and the selective inhibitors of EGFR signaling pathways blocked this effect. Chromatin immunoprecipitation assays revealed that TIP30 negatively regulated EGF-dependent transcriptional activation of CCND1 through a HDAC1-dependent mechanism. In lung adenocarcinoma patients, the level of nuclear TIP30 was inversely correlated with that of EGFR and cyclin D1. These findings suggest that nuclear TIP30-induced downregulation of cyclin D1 transcription antagonizes EGFR signaling and suppresses tumorigenesis.