Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two calgranulins S100A8 and S100A9 were found to be differentially expressed at sites of acute and chronic inflammation. Here we have employed the phorbol ester-induced multistage skin carcinogenesis protocol in mice to determine the expression of both genes in inflamed skin and in skin tumors. We show that expression is coordinately induced by the phorbol ester TPA in epithelial cells as well as infiltrating leukocytes. By comparing S100A8 and S100A9 mRNA levels in wild type and c-Fos deficient mice (c-fos(-/-)) we found that expression is negatively regulated by c-Fos/AP-1. Glucocorticoids, which exhibit potent anti-inflammatory and anti-tumor promoting activities repressed TPA-mediated S100A8 and S100A9 induction in wild type, but not in c-fos(-/-) mice, thus identifying both genes as the first examples of AP-1 target genes whose repression of TPA-induced transcription by glucocorticoids depends on c-Fos. Finally, we show that enhanced expression is not restricted to the initial TPA-induced inflammatory response but is observed at all stages of skin carcinogenesis. These data identify S100A8 and S100A9 as novel, tumor-associated genes and may point to an as yet unrecognized function of both genes in the development of epithelial skin tumors.
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PMID:Calgranulins S100A8 and S100A9 are negatively regulated by glucocorticoids in a c-Fos-dependent manner and overexpressed throughout skin carcinogenesis. 1208 14

Esophageal squamous cell carcinoma (ESCC) is 1 of the most common cancers worldwide. In our study, cDNA microarray comprising 14,803 genes was employed to identify gene-specific expression profile in 6 paired samples of ESCC. Nine genes identified were commonly upregulated and 36 downregulated in tumors, as compared to normal esophageal squamous epithelia. Among these genes, we found that 9 of the altered expression genes were related to arachidonic acid (AA) metabolism, such as annexin-I, annexin-II, S100A8, S100A10, S100P, glutathione peroxidase-3, phosphatidylcholine transfer protein, aldo-keto reductase family 1 and cyclooxygenase-2 (COX-2). To gain insights into the regulation of the AA metabolism pathway involved in the carcinogenesis of ESCC, we investigated the expression of 8 genes related to the AA metabolism by semiquantitative reverse transcript (RT)-PCR and/or Western blot and immunohistochemistry. These genes include annexin-I, annexin-II, COX-2, cyclooxygenase-1 (COX-1) and cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP) and 12-lipoxygenase (12-LOX) (not included in the array data). The expression level of annexin-I, annexin-II was downregulated in esophageal cancer, whereas cPLA(2), FLAP, COX-2, 5-LOX and 12-LOX were upregulated. These data suggested that AA metabolism pathway and its altered expression may contribute to esophageal squamous cell carcinogenesis.
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PMID:The deregulation of arachidonic acid metabolism-related genes in human esophageal squamous cell carcinoma. 1284 69

Chemically induced mouse skin carcinogenesis represents the most extensively utilized animal model to unravel the multistage nature of tumour development and to design novel therapeutic concepts of human epithelial neoplasia. We combined this tumour model with comprehensive gene expression analysis and could identify a large set of novel tumour-associated genes that have not been associated with epithelial skin cancer development yet. Expression data of selected genes were confirmed by semiquantitative and quantitative RT-PCR as well as in situ hybridization and immunofluorescence analysis on mouse tumour sections. Enhanced expression of genes identified in our screen was also demonstrated in mouse keratinocyte cell lines that form tumours in vivo. Self-organizing map clustering was performed to identify different kinetics of gene expression and coregulation during skin cancer progression. Detailed analysis of differential expressed genes according to their functional annotation confirmed the involvement of several biological processes, such as regulation of cell cycle, apoptosis, extracellular proteolysis and cell adhesion, during skin malignancy. Finally, we detected high transcript levels of ANXA1, LCN2 and S100A8 as well as reduced levels for NDR2 protein in human skin tumour specimens demonstrating that tumour-associated genes identified in the chemically induced tumour model might be of great relevance for the understanding of human epithelial malignancies as well.
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PMID:Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. 1624 83

The purpose of this work is to differentiate between the Human papillomaviruses 18 positive (HPV18+) and negative (HPV18-) oral squamous cell carcinomas (OSCC) in oral cancer patients with cancer-associated oral habits (betel quid chewing, cigarette smoking, and alcohol drinking). Both gene and protein expression profiles of HPV18+ and HPV18- OSCC were compared: we then further explored the biological effect of HPV in oral cancer. Suppression subtraction hybridization (SSH), clinical proteomics analysis, and immunohistochemistry (IHC) staining were carried out in the HPV18+ and HPV18- OSCC groups. HPV typing detection revealed that 11 OSCC tissues from 82 patients were positive for HPV18. The SSH experiment showed that 4 cancer-associated genes were highly transcribed within 11 cDNA libraries of HPV18+ OSCC, including poly(ADP-ribose)polymerase I (PARP1), replication protein A2 (RPA2), S100A8, and S100A2. Clinical proteomics analysis indicated that there was over 10-fold overexpression of Stratifin, F-actin capping protein alpha-1 subunit (CapZ alpha-1), Apolipoprotein A-1 (ApoA-1), Heat-shock protein 27 (HSP27), Arginase-1, p16INK4A, and S100 calcium-binding protein A8 (S100A8) in HPV18+ OSCC. Interestingly, the results from SSH and protemics analysis showed that S100A8 was overexpressed in HPV18+ OSCC. Moreover, IHC staining demonstrated that S100A8 was up-regulated in HPV18+ OSCC tissues. Our results suggest that S100A8 plays an important role in oral carcinogenesis following HPV18 infection; therefore, S100A8 may be a powerful biomarker of HPV18 as well as a potential therapeutic target for HPV18+ OSCC patients. The study is the first to identify S100A8 as a biomarker in HPV-associated cancer. Furthermore, this is also the first study to discover a biomarker by combining SSH, clinical proteomics, and IHC stain analysis in oral cancer-associated research.
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PMID:S100A8 is identified as a biomarker of HPV18-infected oral squamous cell carcinomas by suppression subtraction hybridization, clinical proteomics analysis, and immunohistochemistry staining. 1745 Dec 65

The S100 gene family, which is composed of at least 24 members carrying the Ca2+ binding EF-hand motif, has been implicated in both intracellular and extracellular functions, including enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis, cell growth and cell differentiation. Altered S100 protein levels are associated with a broad range of diseases, including cardiomyopathy, inflammatory and immune disorders, neurodegenerative disorders and cancer. Although the precise role of S100 protein in carcinogenesis is poorly understood, it seems that formation of homo- and hetero-dimers, binding of Ca2+ and interaction with effector molecules are essential for the development and progression of many cancers. Several studies have suggested that S100 proteins promote cancer progression and metastasis through cell survival and apoptosis pathways. In animal models of bladder cancer, several S100 proteins are differentially expressed in bladder tumors relative to normal urothelium. In human bladder cancer, overexpression of S100A4, S100A8 or S100A11 are associated with stage progression, invasion, metastasis and poor survival. This review summarizes these findings and evaluates their implications for human bladder cancer management.
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PMID:The S100 proteins for screening and prognostic grading of bladder cancer. 1752 80

Squamous cell carcinoma in the lung originates from bronchial epithelial cells that acquire increasingly abnormal phenotypes. Currently, no known biomarkers are clinically efficient for the early detection of premalignant lesions and lung cancer. We sought to identify secreted molecules produced from squamous bronchial epithelial cells cultured with organotypic culture methods. We analyzed protein expression patterns in the apical surface fluid (ASF) from aberrantly differentiated squamous metaplastic normal human tracheobronchial epithelial (NHTBE) and mucous NHTBE cells. Comparative two-dimensional PAGE analysis revealed 174 unique proteins in the ASF of squamous NHTBE cells compared with normal mucociliary differentiated NHTBE cells. Among them, 64 well-separated protein spots were identified by liquid chromatography-tandem mass spectrometry, revealing 22 different proteins in the ASF from squamous NHTBE cells. Expression of six of these proteins [SCC antigen 1 (SCCA1), SCC antigen 2 (SCCA2), S100A8, S100A9, Annexin I, and Annexin II] in the squamous NHTBE cells was further confirmed with immunoblot analysis. Notably, SCCA1 and SCCA2 were verified as being expressed in squamous metaplastic NHTBE cells but not in normal mucous NHTBE or normal bronchial epithelium. Moreover, SCCA1 and SCCA2 expression increased in in vitro lung carcinogenesis model cell lines with increasing malignancy. In summary, we identified proteins that are uniquely secreted from squamous metaplastic primary human bronchial epithelial cells cultured by the organotypic air-liquid interface method. These ASF proteins may be used to detect abnormal lesions in the lung without collecting invasive biopsy specimens.
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PMID:Proteomics-based identification of proteins secreted in apical surface fluid of squamous metaplastic human tracheobronchial epithelial cells cultured by three-dimensional organotypic air-liquid interface method. 1763 65

Human leukocyte antigen B (HLA-B), a novel member of the NF-kappaB signal pathway in laryngeal squamous cell carcinoma (LSCC), mediates immunological surveillance of tumor cells by presenting peptides to cytotoxic T-lymphocytes (CTLs) together with S100 calcium binding protein A8 (S100A8). The objective of this study was to investigate the molecular mechanism of HLA-B and S100A8 in laryngeal carcinogenesis. Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay and cell invasion in vitro were used to detect the biological effect of the Hep2 cell line induced by HLA-B RNA interference. RT-PCR and Western blotting were applied to evaluate the expression level of the S100A8 gene after HLA-B RNA interference. Our results showed that HLA-B had negative effects on Hep2 cells by inhibiting apoptosis and cell invasion while decreasing cell proliferation. Additionally, the expression level of HLA-B and S100A8 in LSCC were down-regulated after HLA-B RNA interference. The abnormal expression of HLA-B is thus relevant to the biological effect of laryngeal carcinoma and participates in the NF-kappaB signal pathway partly by regulating the expression of the S100A8 gene.
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PMID:HLA-B gene participates in the NF-kappaB signal pathway partly by regulating S100A8 in the laryngeal carcinoma cell line Hep2. 1849 50

Patients with inflammatory bowel diseases are at increased risk for colorectal cancer, but the molecular mechanisms linking inflammation and cancer are not well defined. We earlier showed that carboxylated N-glycans expressed on receptor for advanced glycation end products (RAGE) and other glycoproteins mediate colitis through activation of nuclear factor kappa B (NF-kappaB). Because NF-kappaB signaling plays a critical role in the molecular pathogenesis of colitis-associated cancer (CAC), we reasoned that carboxylated glycans, RAGE and its ligands might promote CAC. Carboxylated glycans are expressed on a subpopulation of RAGE on colon cancer cells and mediate S100A8/A9 binding to RAGE. Colon tumor cells express binding sites for S100A8/A9 and binding leads to activation of NF-kappaB and tumor cell proliferation. Binding, downstream signaling and tumor cell proliferation are blocked by mAbGB3.1, an anti-carboxylate glycan antibody, and by anti-RAGE. In human colon tumor tissues and in a mouse model of CAC, we found that myeloid progenitors expressing S100A8 and S100A9 infiltrate regions of dysplasia and adenoma. mAbGB3.1 administration markedly reduces chronic inflammation and tumorigenesis in the mouse model of CAC and RAGE-deficient mice are resistant to the onset of CAC. These findings show that RAGE, carboxylated glycans and S100A8/A9 play essential roles in tumor-stromal interactions, leading to inflammation-associated colon carcinogenesis.
Carcinogenesis 2008 Oct
PMID:RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. 1868 72

Chronic inflammation is a complex process that promotes carcinogenesis and tumor progression; however, the mechanisms by which specific inflammatory mediators contribute to tumor growth remain unclear. We and others recently demonstrated that the inflammatory mediators IL-1beta, IL-6, and PGE(2) induce accumulation of myeloid-derived suppressor cells (MDSC) in tumor-bearing individuals. MDSC impair tumor immunity and thereby facilitate carcinogenesis and tumor progression by inhibiting T and NK cell activation, and by polarizing immunity toward a tumor-promoting type 2 phenotype. We now show that this population of immature myeloid cells induced by a given tumor share a common phenotype regardless of their in vivo location (bone marrow, spleen, blood, or tumor site), and that Gr1(high)CD11b(high)F4/80(-)CD80(+)IL4Ralpha(+/-)Arginase(+) MDSC are induced by the proinflammatory proteins S100A8/A9. S100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-kappaB pathway, and promote MDSC migration. MDSC also synthesize and secrete S100A8/A9 proteins that accumulate in the serum of tumor-bearing mice, and in vivo blocking of S100A8/A9 binding to MDSC using an anti-carboxylated glycan Ab reduces MDSC levels in blood and secondary lymphoid organs in mice with metastatic disease. Therefore, the S100 family of inflammatory mediators serves as an autocrine feedback loop that sustains accumulation of MDSC. Since S100A8/A9 activation of MDSC is through the NF-kappaB signaling pathway, drugs that target this pathway may reduce MDSC levels and be useful therapeutic agents in conjunction with active immunotherapy in cancer patients.
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PMID:Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. 1880 69

Comparative microarray analyses provided insight into understanding transcript changes during cancer progression; however, a reproducible signature underlying breast carcinogenesis has yet to be little available. We utilized gene expression profiling to define molecular signatures associated with transformation and cancer progression in a series of isogenic human breast cancer cell lines including a normal, benign, noninvasive and invasive carcinoma. Clustering analysis revealed four distinct expression patterns based on upregulation or downregulation patterns. These profiles proved quite useful for describing breast cancer tumorigenesis and invasiveness. Downregulation of TNFSF7, S100A4, S100A7, S100A8, and S100A9 (calcium-binding protein family), and upregulation of kallikrein-5 and thrombospondin-1 were associated with transformation and progression of breast cancer cells. Importantly, downregulation of the genes was reversed by treatment with silencing inhibitors, implying the potential roles of epigenetic inactivation in breast carcinogenesis. Exogenous expressions of S100A8 and S100A9 inhibit growth in benign and noninvasive carcinoma cells, suggesting their negative role in cell proliferation. The data presented here may facilitate the identification and functional analyses of prognostic biomarkers for breast cancer.
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PMID:Molecular signatures associated with transformation and progression to breast cancer in the isogenic MCF10 model. 1880 27


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