Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Annexin I is a phospholipid and actin binding protein which may play a role in signal transduction to the cytoskeleton. Previous work reported the differential expression of annexin I mRNA among rat adenocarcinoma cell lines of various metastatic potential (MTLn3, MTLn2, MTC.4: highest to lowest, respectively) (Pencil et al. 1993, Breast Cancer Res Treat, 25, 165-74). This relationship has been extended to the protein level in in vitro cultures using Western blotting and flow cytometry. Annexin I protein levels in MTLn3 cells are 3- to 5-fold higher than in MTC.4 cells. The weakly metastatic cell line MTLn2 shows levels 1.5- to 2.5-fold higher than MTC.4. In vivo tumors were produced by injecting 1 x 10(6) cells into mammary fat pads of syngeneic rats and necropsies were performed 40 days later. Semiquantitative immunohistochemical color image analysis was performed using a polyclonal rat annexin I specific antibody. Annexin I protein expression was highest in lung metastases of MTLn3, at 8-fold the levels observed in the MTC.4 primary tumors. MTLn3 cells in the primary tumor had an annexin I specific optical density 3-fold higher than that of cells in the MTC.4 primary tumor. MTLn2 primary tumors had an annexin I specific optical density 1.5-fold higher than MTC.4. A proportion of human mammary adenocarcinomas also have positive annexin I immunoreactivity, often with more uniform annexin I staining in the lymph node metastases. These results suggest that there may be survival advantages for nascent metastatic cells with high annexin I levels.
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PMID:Elevated levels of annexin I protein in vitro and in vivo in rat and human mammary adenocarcinoma. 951 92

Smokeless tobacco usage is a growing public health concern in the United States. Epidemiological evidence shows a correlation between use of chewing tobacco, lesions of the oral cavity and the incidence of oral and other cancers. However, the molecular mechanism(s) underlying the oral cancer causation are yet unknown. The major constituents of tobacco are known to cause inflammation, DNA damage and cell death. We propose modulation of inflammatory mediators by smokeless tobacco as a novel mechanism for the development of oral cancer. Exposure of hamster cheek pouches to smokeless tobacco extract (STE) results in cleavage of the anti-inflammatory peptide from the anti-inflammatory protein annexin I. Annexin I is produced from cultured oral epithelial cells and its expression is modulated by STE. We further show that STE exposure of oral epithelial cells results in upregulation of the pro-inflammatory protein COX-2. COX-2 is also upregulated in immortalized human oral epithelial cells, human squamous cell carcinoma cells and in primary tumor tissues from head and neck cancer. In summary, we find that exposure to smokeless tobacco results in loss of the anti-inflammatory activity of annexin I and upregulation of the pro-inflammatory COX-2 in oral cells. The dual effect of these regulatory events leads the cells down the carcinogenic pathway.
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PMID:Modulation of annexin I and cyclooxygenase-2 in smokeless tobacco-induced inflammation and oral cancer. 1287 Jun 56