Expression of BCL10 in cervical cancer has a role in the regulation of cell growth through the activation of NF-κB-dependent cyclin D1 signaling
Journal
Gynecologic Oncology
Journal Volume
126
Journal Issue
2
Pages
245-251
Date Issued
2012
Author(s)
Abstract
Objective: We recently characterized the molecular linkage that directs both BCL10 overexpression and nuclear translocation in response to inflammation-related NF-κB signaling pathway. Since NF-κB activation has been shown to occur in the pathogenesis of cervical cancer, we sought to investigate whether BCL10 possesses clinical significance in relation to cervical cancer. Methods: Four cervical cancer cell lines (C33A, SiHa, HeLa, and CaSki) were used in this study. The DNA-binding activity of NF-κB was determined by the luciferase assay. The expression of BCL10, NF-κB, and cyclin D1 in tumor cells from an array of 182 tissue samples was examined using immunohistochemical staining. Results: We transfected four cervical cancer cell lines with BCL10 small interfering RNA (siRNA), and discovered that the down-regulation of BCL10 inhibited the viability of these cervical cancer cells through G1 arrest. BCL10 siRNA treatment inhibited the expression of p-IKKβ and p-IκB, and also down-regulated both NF-κB activation cyclin D1, its downstream cell cycle protein. Our results reveal that cervical cancer had a higher rate of positive cytoplasmic staining (74.1%, 123/166) than either carcinoma in situ (50.0%, 3/6) or normal cervix (0.0%, 0/10); and that poorly differentiated cancer had a higher rate of cytoplasm staining (80.7%, 71/88) than moderately differentiated (75.4%, 43/57) and well differentiated (40%, 4/10) carcinoma. Furthermore, nuclear expression of BCL10 was closely associated with NF-κB activation (p < 0.001) and cyclin D1 expression (p < 0.001). Conclusions: Our findings indicate that BCL10 plays an important role in controlling the growth of cervical cancer cells through NF-κB dependent cyclin D1 regulation. ? 2012 Elsevier Inc. All rights reserved.
SDGs
Other Subjects
cell cycle protein; cyclin D1; DNA; I kappa B; I kappa B kinase beta; immunoglobulin enhancer binding protein; luciferase; protein bcl 10; small interfering RNA; adult; article; carcinogenesis; carcinoma in situ; cell growth; cell viability; controlled study; cytoplasm; DNA binding; down regulation; female; flow cytometry; G1 phase cell cycle checkpoint; gene expression; gene overexpression; gene translocation; human; human cell; human tissue; immunohistochemistry; major clinical study; priority journal; signal transduction; tissue microarray; uterine cervix cancer; Western blotting; Adaptor Proteins, Signal Transducing; Cell Culture Techniques; Cell Growth Processes; Cell Line, Tumor; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Immunohistochemistry; NF-kappa B; RNA, Small Interfering; Signal Transduction; Transfection; Uterine Cervical Neoplasms
Type
journal article