Lack of modulatory function of coding nucleotide polymorphism S100A2_185G&gt;A in oral squamous cell carcinoma

Tsai, Wen Chun; Lin, Yuan-Chih; Tsai, Sen Tien; Shen, Wenhao; Chao, Tai‐Ling; Lee, S. L.; Wu, Li-Wha

doi:10.1111/j.1601-0825.2010.01738.x

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…The encoded proteins contain two EF-hand calcium-binding helix-loop-helix motifs. Each member contains two EF-hands connected by a central hinge, which is S100 family-specific in the N-terminus and canonical in C-terminus (4). Overexpression of the S100 calcium-binding protein A4 [S100A4, also known as Mts1 (metastasis-associated gene), p9Ka, 18A2, pEL98, 42A, CAPL and calvasculin] of the S100 protein family has been shown to control cell cycle progression and modulate intercellular adhesion, as well as invasive and metastatic properties of cancer cells (5).…”

Section: Introductionmentioning

confidence: 99%

S100 calcium-binding protein A4 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

2013

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Overexpression of the S100 calcium-binding protein A4 (S100A4) is involved in epithelial-to-mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity and cancer metastasis. Here, we elucidated the role of S100A4 in tumorigenesis and progression of gastric carcinomas. S100A4 expression in gastric carcinomas, adenomas and adjacent non-neoplastic mucosa was analyzed by immunohistochemical, real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) and western blot analyses, and was correlated with various clinicopathological parameters. S100A4 protein expression was increased gradually in the following order: gastritis (19.2%), intestinal metaplasia (IM; 23.3%), dysplasia (34.9%) and carcinoma (55.2%; P<0.001). S100A4 was positively correlated with tumor size, depth of invasion, lymphatic invasion, lymph node metastasis and tumor-node-metastasis (TNM) staging (P<0.05), but not with the age and gender of the carcinoma patients (P>0.05). Intestinal-type (IT) carcinomas showed a higher S100A4 expression than diffuse-type (DT) carcinomas (P<0.001). S100A4 mRNA expression also increased in the following order: gastritis < IM < dysplasia < carcinoma (P<0.05). S100A4 overexpression was observed in gastric carcinomas with a larger diameter, deeper invasion, lymph node metastasis and in IT carcinoma (P<0.05). Univariate analysis using the Kaplan-Meier method indicated a lower cumulative survival rate for patients with weak or moderate S100A4 expression compared with patients not expressing S100A4 (P<0.001). Multivariate analysis using Cox's proportional hazard model demonstrated that depth of invasion, lymphatic or venous invasion, lymph node metastasis, TNM staging and S100A4 expression were independent factors for poor patient prognosis (P<0.05). In conclusion, S100A4 upregulation is positively associated with the pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. S100A4 may be a promising marker indicative of the aggressive behavior and prognosis of gastric carcinomas.

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Section: Introductionmentioning

confidence: 99%

S100 calcium-binding protein A4 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

2013

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“…In addition, the CAL27 cell line contains a nonsense mutation in the SMAD4 gene, while SCC15 cells were found to harbor a missense mutation in SMAD2 -both signal TGF-β transduction proteins [61]. Finally, both CAL27 and SCC15 cells contain a single nucleotide polymorphism in the S100A2 gene, a calcium-binding tumor suppressor protein, although this does not appear to alter their propensity for growth, migration or invasion [62]. However, a growing body of evidence demonstrates that deregulation and reduced expression of key tumor suppressors, such as p16, in these cell lines may, in fact, be the result of hyper methylation -providing further justification to elucidate the interconnected roles of dietary components and transcriptional regulation in the growth and progression of oral cancers [63][64][65].…”

Section: Discussionmentioning

confidence: 97%

“…These SPE components include, but are not limited to, phytates (inositol hexaphosphate), oligosaccharides, saponins, Kunitz inhibitor and Bowman-Birk Inhibitor (BBI) [68]. Some previous studies have demonstrated that saponins were capable of exerting growth inhibiting effects on colon cancer cell lines in vitro [62,69,70]. In addition, other studies have demonstrated cytotoxicity and apoptotic effects on oral cancers in vitro using saponins [71][72][73].…”

Section: Discussionmentioning

confidence: 99%

Interactive effects of 1, 25-dihydroxyvitamin D3 and soy protein extract (SPE) on oral cancer growth in vitro: evidence for potential functional relationships.

Kingsley

Keiserman²,

Bergman

2013

FFHD

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Background: Previous studies have found specific soy isoflavones (Genistein, Daidzein, Glycitein) demonstrate anti-tumor properties against several cancer types, including oral cancer. Few studies have evaluated whole soy extract, containing a combination of these isoflavones and other bioreactive compounds, which may function synergistically and more effectively against oral cancers. Preliminary work by this group has now demonstrated whole soy protein extract (SPE) inhibits oral cancer cell growth specifically and selectively, through independent cell-cycle and apoptotic pathways. However, more recent evidence now suggests that ingestion of vitamin D3, either in dietary foods or supplements may potentiate the activity of soy components and their anti-tumor effects.Objective: The primary goal of this study was to investigate the interactive and inter-connected effects of 1, 25-dihydroxyvitamin D3 administration with the anti-proliferative effects of whole soy protein extract (SPE) on oral cancer and normal cell lines in vitro.Methods: Three oral squamous cell carcinoma cell lines (SCC15, SCC25, and CAL27) were treated with 1, 25-dihydroxy Vitamin D3 at physiological concentrations (10-125 nmol). Cell growth was then compared with cell treatment using soy protein extract (SPE) within the normal physiologic range (0 - 10 μM/L). Interactive effects were then evaluated using co-administration of SPE and 1, 25-dihydroxy Vitamin D3. Quantitative RT-PCR was performed at various time points to determine any changes in mRNA expression for key cell cycle and apoptotic signaling pathway regulators, including p53, c-myc, ornithine decarboxylase (ODC), caspase-2, caspase-8, and bax. Results: Administration of 1, 25-dihydroxy Vitamin D3 induced distinct dose-dependent, growth-inhibitory effects in all three oral cancer cell lines examined. These inhibitory effects were comparable to the overall range of growth inhibition induced by SPE. However, the combined effects of co-administration were far greater, suggesting the presence of synergistic relationships between these components. In addition, these results indicate that either treatment alone appeared to modulate mRNA expression of oral cancer cell-cycle promoters c-myc and ODC, as well as the caspase-dependent apoptosis pathway, while only 1, 25-dihydroxy Vitamin D3 administration appeared to influence the bax pathway. Conclusion: These results suggest that co-administration with 1, 25-dihydroxy Vitamin D3 and SPE may enhance their anti-tumor effects. This study may help to explain, in part, why balanced diets rich in fruits, vegetables, and soy protein, are associated with protection against development and progression of oral cancers, although further study is needed to develop specific public health recommendations for oral cancer treatment and prevention.Key words: vitamin D, soy extract, whole soy protein, oral cancer, growth inhibition.

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“…The CAL27 cell line contains a nonsense mutation in the SMAD4 gene, while SCC15 cells were found to harbor a missense mutation in SMAD2 - both signal TGF-β transduction proteins [61]. In addition, both CAL27 and SCC15 cells contains a single nucleotide polymorphism in the S100A2 gene, a calcium-binding tumor suppressor protein, although this did not appear to alter their propensity for growth, migration or invasion [62]. However, a growing body of evidence demonstrates that dysregulation and reduced expression of key tumor suppressors, such as p16, in these cell lines may, in fact, be the result of hypermethylation - providing further justification to elucidate the interconnected roles of FA bioavailability and utilization may play in the growth and progression of oral cancers [63-65].…”

Section: Discussionmentioning

confidence: 99%

Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation

et al. 2012

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BackgroundAlthough the primary risk factors for developing oral cancers are well understood, less is known about the relationship among the secondary factors that may modulate the progression of oral cancers, such as high-risk human papillomavirus (HPV) infection and folic acid (FA) supplementation. This study examined high-risk HPV and FA supplementation effects, both singly and in combination, to modulate the proliferative phenotypes of the oral cancer cell lines CAL27, SCC25 and SCC15.ResultsUsing a comprehensive series of integrated in vitro assays, distinct effects of HPV infection and FA supplementation were observed. Both high-risk HPV strains 16 and 18 induced robust growth-stimulating effects in CAL27 and normal HGF-1 cells, although strain-specific responses were observed in SCC25 and SCC15 cells. Differential effects were also observed with FA administration, which significantly altered the growth rate of the oral cancer cell lines CAL27, SCC15, and SCC25, but not HGF-1 cells. Unlike HPV, FA administration induced broad, general increases in cell viability among all cell lines that were associated with p53 mRNA transcriptional down-regulation. None of these cell lines were found to harbor the common C677T mutation in methylenetetrahydrofolate reductase (MTHFR), which can reduce FA availability and may increase oral cancer risk.ConclusionIncreased FA utilization and DNA hypermethylation are common features of oral cancers, and in these cell lines, specifically. The results of this study provide further evidence that FA antimetabolites, such as Fluorouracil (f5U or 5-FU) and Raltitrexed, may be alternative therapies for tumors resistant to other therapies. Moreover, since the incidence of oral HPV infection has been increasing, and can influence oral cancer growth, the relationship between FA bioavailability and concomitant HPV infection must be elucidated. This study is among the first pre-clinical studies to evaluate FA- and HPV-induced effects in oral cancers, both separately and in combination, which provides additional rationale for clinical screening of HPV infection prior to treatment.

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Lack of modulatory function of coding nucleotide polymorphism S100A2_185G>A in oral squamous cell carcinoma

Abstract: The coding sequence polymorphism S100A2_185G>A had no regulatory role in S100A2-mediated tumor suppression in oral cancer.

Cited by 5 publications

References 25 publications

S100 calcium-binding protein A4 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

S100 calcium-binding protein A4 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas

Interactive effects of 1, 25-dihydroxyvitamin D3 and soy protein extract (SPE) on oral cancer growth in vitro: evidence for potential functional relationships.

Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation

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