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B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter. In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Placenta growth factor (PIGF) is associated with the progression and prognosis of oral cancer. MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PIGF) protein or mRNA expression in human gingival epithelial S-G cells. RESULTS: Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PIGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PIGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-L-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and P13-K inhibitor LY294002, significantly reduced arecoline-induced PIGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PIGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 µM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 µM curcumin completely blocked arecoline-induced PIGF mRNA expression. CONCLUSION: Arecoline-induced PIGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis. [ABSTRACT FROM AUTHOR]

Expression of ras p21 oncoproteins was examined in histological sections of oral squamous cell carcinoma (SCC), epithelial dysplasia, epithelial hyperkeratosis and normal oral mucosa using antibodies to ras p21 with an immunoperoxidase technique. Ras p2l-positive staining was found in 47 of 51 (92.2%) cases of oral SCC, 4 of 4 (100%) cases of epithelial dysplasia, 7 of 7 (100%) cases of epithelial hyperkeratosis, and 1 of 6 (16.7%) cases of normal oral mucosa. The positive staining rate of ras p21 in oral SCC, epithelial dysplasia or epithelial hyperkeratosis was significantly higher than that in normal oral mucosa (P<0.05). No correlation was found between fas p21 expression and patient age, tumour location, tumour size, clinical staging or histological differentiation of SCC. However, a significant positive correlation was found between ras p21 expression and patinsts' sex (P<0.05) or regional lymph node status (P<0.05). A significant positive correlation was also discovered between fas p21 expression and patients' smoking habits (P<0.01), as well as daily or total betel quid (BQ) consumption (P<0.05). Of the 47 immunostain-positive SCC patients, specimens from 6 patients were also obtained after chemotherapy, when ras p21 expression was found to be reduced. These results indicate that ras p21 overexpression may play an important role in the initiation and progression of oral SCCs in patients who are smokers and BQ chewers. [ABSTRACT FROM AUTHOR]