The Regulation Mechanism of B Cell Lymphoma/Leukemia 10 in Oral Squamous Cell Carcinoma
Date Issued
2012
Date
2012
Author(s)
Wu, Tai-Sheng
Abstract
Purpose:
B-cell lymphoma/leukemia 10 (BCL10) is elevated in advanced oral squamous cell carcinoma (OSCC) patient and positive correlated with TNM stage. However, the regulatory mechanism of BCL10 in OSCC progression is completely unknown.
Methods:
SAS, CA9-22, HSC3, TW2.6, and Cal27 oral cancer cell lines were used as in vitro models to investigate cell phenotypes, including invasion, migration, and proliferation by BCL10 shRNA knockdown. Wound healing analysis and Boyden chamber assay were performed to check migration and invasion abilities. Proliferation ability was identified by MTT assay, colony formation, and flow cytometry in vitro. Mice were s.c. injected with shBCL10-silencing or vector control SAS cells to measure tumorigenicity.
Results:
BCL10 expression was positively correlated with invasion ability in OSCC cells. Transiently transfected SAS and CA9-22 cells with shBCL10 knockdown plasmid significantly reduced migration, invasion ability, and proliferation ability, approximately 40 % reduction of migration, 40 % reduction of invasion, and 30 % reduction of proliferation abilities in SAS and CA9-22 cells, compared to vector control cells (all P < 0.05). Furthermore, we established shBCL10-stable transfectants in SAS and CA9-22 cells, and found that silencing BCL10 could significantly down-regulated migration, invasion, and proliferation abilities, approximately 40% reduction of migration, invasion ,and proliferation (all P < 0.05). Cell cycle arrest was also detected in BCL10-silenced transfectants, cells were 20 % increase of G0/G1 phase and 10 % decrease of G2/M phase in SAS/shBCL10 and CA9-22/shBCL10 transfectants, compared to vector control cells (P < 0.05). Additionally, we performed high throughput mRNA microarray analysis and identified a downstream effecter S100P, a member of S100 protein family after transiently transfected with S100P expression plasmid could restore migration, invasion, and proliferation abilities in shBCL10-stable transfectant conformed (all P < 0.05). Moreover, we re-expressed S100P in shBCL10-stable transfectant could significantly restore the migration, invasion, and proliferation ability, approximately 70% induction of migration and invasion, and 30% induction of proliferation abilities in SAS/shBCL10 cells (P < 0.05). Tumor volume was decreased in s.c. injected shBCL10-stable transfectant, and restored S100P expression reversed BCL10- enhanced tumorigenicity in vivo.
Conclusion:
BCL10 promotes OSCC progression via induced S100P-dependent signaling.
Subjects
oral cancer
invasion
migration
proliferation
BCL10
SDGs
Type
thesis
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