title: Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.
abstract: Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.
authors: Departments of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Kiyoshi
authors: K
authors: Takagi
authors: Yasuhiro
authors: Y
authors: Miki
authors: Sota
authors: S
authors: Tanaka
authors: Chiaki
authors: C
authors: Hashimoto
authors: Mika
authors: M
authors: Watanabe
authors: Hironobu
authors: H
authors: Sasano
authors: Kiyoshi
authors: K
authors: Ito
authors: Takashi
authors: T
authors: Suzuki
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000080866:Nucleobindins; D011379:Prognosis; D021381:Protein Transport; D034622:RNA Interference; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C000630650:NUCB2 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins