Objective: The protein interacting with carboxyl terminus-1 (PICT-1) gene has been implicated as a tumor suppressor gene, and its alterations have been reported in several cancers. This study investigated the association of PICT-1 alterations with endometrial carcinogenesis.
Methods: We analyzed the entire coding region of the PICT-1 gene using polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing to examine PICT-1 mutations in endometrial cancer. Western blotting and immunohistochemical staining were performed to analyze the protein expression and cellular localization of PICT-1 in endometrial cancer cell lines and patient samples.
Results: The codon 389 polymorphism of PICT-1 increased the risk of endometrial cancer. Interestingly, 2 of 13 endometrial cancers somatically acquired this mutation compared to normal counterparts. Immunohistochemical staining revealed lower levels of PICT-1 in samples from atypical endometrial hyperplasia and endometrial cancer tissues compared to normal endometrial tissues (p < 0.01). This decrease in PICT-1 expression was significantly correlated with histological grade and lymph node metastasis (p < 0.05).
Conclusions: The findings of this study suggest that disruption of PICT-1 protein expression and codon 389 polymorphism can contribute to the pathogenesis or neoplastic progression of endometrial cancer.
Keywords: Endometrial carcinogenesis; PICT-1; Polymorphism; Protein reduction; Risk factor.
© 2018 S. Karger AG, Basel.