Meaning of tumor protein 53-induced nuclear protein 1 in the molecular mechanism of gemcitabine sensitivity

Abstract

Stress proteins of the pancreas, such as tumor protein 53-induced nuclear protein 1 (TP53INP1), are important factors in the invasion and metastasis of pancreatic cancer. TP53INP1 is a pro-apoptotic factor and is transcriptionally regulated in p53-dependent and -independent manners. A previous study proved that gemcitabine induces TP53INP1 expression in pancreatic cancer cells and the pancreatic cancer cell line (PANC-1). The present study aimed to clarify the association between TP53INP1 and gemcitabine sensitivity. The expression of TP53INP1 and its related factors, such as cell growth and cell cycle status in TP53INP1-knockout mouse embryonic fibroblasts [TP53INP1-/--mouse embryonic fibroblasts (MEFs)] to those in wild-type counterparts (TP53INP1+/+-MEFs) were compared. Flow cytometric analysis demonstrated no difference of the checkpoint function in TP53INP1-/--MEFs and TP53INP1+/+-MEFs when exposed to 10 ng/ml of gemcitabine. No significant difference was found in the level of p53 expression in the cell types, although the base level and gemcitabine-induced expression of p21 were significantly decreased in TP53INP1-/--MEFs, compared to those in wild-type counterparts. Results showed that gemcitabine induced the p21 expression in TP53INP1+/+-MEFs, although not in TP53INP1-/--MEFs. However, their respective cell-cycle checkpoints were not different. Therefore, TP53INP1 was found to be associated with drug sensitivity through control of the cell cycle.