Masafumi Yoshimoto1, Aoi Tokuda1, Kunihiko Nishiwaki2, Kazuo Sengoku2, Yuji Yaginuma1. 1. Department of Oncology, Graduate School of Health Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. 2. Department of Obstetrics and Gynecology, Asahikawa Medical University, Asahikawa, Japan.
Abstract
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.
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.