S100 protein A8 and A9 naturally form a stable heterocomplex. Recently, we have proved that S100A9 overexpression in various adenocarcinomas is associated with poor tumor differentiation. In this study, we examined the relationship between the expression of each protein and the pathological parameters that reflect the aggressiveness of carcinoma, in invasive ductal carcinoma (IDC) of the breast. Serial paraffin-embedded tissue sections from 101 IDC cases were immunostained with respective monoclonal antibodies, and the results were as follows: 1) A positive correlation of immunoreactivity between S100A8 and S100A9 was noticed (r=0.873 and P<0.0001); 2) The percentage of S100A9-positive tumor cells was higher than that of S100A8-positive tumor cells (P<0.001), and S100A8 alone was not detected in any case; 3) Overlap between S100A8 and S100A9 staining patterns was found in the corresponding tissue areas, but S100A9 positivity was also observed in S100A8-negative tumor cells; 4) The immunopositivity for each protein also correlated with the mitotic activity, MIB-1 index, HER2 overexpression, node metastasis, and poor pT categories and pStage (P<0.05); 5) Co-expression of both proteins was associated with poor tumor differentiation, vessel invasion, node metastasis, and poor pStage (P<0.05). Furthermore, co-expression of the proteins was also observed in MCF-7 cells, and it was suggested that the immunolocalization is related with cell cycle. Our conclusions are as follows: 1) It is suggested that S100A8 is S100A9-dependently expressed and acquires the protein stability by S100A8/A9 heterocomplex formation; 2) S100A8 and S100A9 overexpression should be considered marker of poor prognosis in IDC.

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This study aimed to analyze expression of S100A10, annexin II and B-FABP genes in renal cell carcinoma (RCC) and their potential value as tumor markers. Furthermore, any correlation between the gene expression and prognostic indicators of RCC was analyzed. Expression of each gene was estimated by RT-PCR in the nonneoplastic (normal) and tumorous parts of resected kidney samples. Also, each antigen was immunostained in RCC and normal kidney tissues. Expression of the S100A10 gene averaged 2.5-fold higher in the tumor than that in the normal tissues (n = 47), after standardization against that of β β β β-actin. However, expression of annexin II, a natural ligand of S100A10, was only 1.64-fold higher. In the tissue sections of RCC, S100A10 and annexin II were immunostained in membranes. In the normal renal epithelia, however, both antigens were stained in the Bowman's capsule and the tubules from Henle's loop through the collecting duct system, but not in the proximal tubules, from where most RCC are derived. In contrast, expression of the B-FABP gene was 20-fold higher in the tumor. No B-FABP was immunohistochemically detected in normal kidney sections, but it was stained in the cytoplasm of RCC tissue sections. S100A10 and B-FABP genes were overexpressed regardless of nuclear grade and stage of RCC. Immunopositivity in RCC tissues (n = 13) was 100% for S100A10 and annexin II, and 70% for B-FABP; however, no clear relationship was observed in either antigen with nuclear grade and stage. It was found that all three performed well as RCC markers. B-FABP was most specific to RCC, as it was expressed little in normal kidney tissues. (Cancer Sci 2007; 98: 77-82) W e have previously described the overexpression of S100A10 in renal cell carcinoma (RCC) cells compared with the normal human kidney cDNA library.(1) Such overexpression has been confirmed in RCC and non-neoplastic (normal) tissues in surgically resected kidneys (n = 7).(1,2) S100A10 is a member of the S100 family of proteins that are small acidic calcium-binding proteins with two helix-loop-helix EF-hand motifs. Twenty human S100 family members are expressed in a cell-and tissue-specific manner, and are responsible for a variety of cellular processes including cell proliferation and differentiation.(3,4) Sixteen of their genes (designated S100A1-S100A16) are clustered on the chromosome 1q21 region, where a number of chromosomal abnormalities occur with neoplasias.(4) S100A10 forms a heterotetramer with annexin II (S100A10) 2 (annexin II) 2 , and the complex localizes in the extracellular membrane of various cancer cells. In the present study, we estimated the gene expression of S100A10 and annexin II by reverse transcription-polymerase chain reaction (RT-PCR) in a larger number of surgically resected RCC samples (n = 47) after standardization for the expression of β-actin in each sample. Then we immunohistochemically investigated the expression of S100A10 and annexin II in RCC and normal kidney tissues (n = 13). The extracellular S100A10/ annexin II complex f...

Tea catechins exert many biological effects, including anticancer and antibacterial activities. Also, it is reported that some plant flavonoids exhibit estrogenic activity. In this study, we investigated estrogenic or antiestrogenic activities of catechins in HeLa cells transiently transfected with an estrogen response element (ERE)-regulated luciferase reporter and an estrogen receptor (ER) alpha or ERbeta expression vector. Catechins alone did not induce luciferase (luc) activity in either of the ERs. Addition of 17beta-estradiol (E2) plus epicatechin gallate (ECG) or epigallocatechin gallate (EGCG) at 5 x 10(-6) M resulted in significant decreases in the ERalpha-mediated luc activity compared with that of E2 alone. On the contrary, lower concentrations significantly increased the E2-induced luc activity. Similar effects were observed with tamoxifen. The ERbeta-mediated estrogenic activities were stimulated by catechins. In conclusion, some catechins, particularly EGCG, were antiestrogenic for ERalpha at higher doses, and co-estrogenic for ERalpha at lower doses and for ERbeta. The lower doses were found in human plasma after tea-drinking. In addition, some catechins may be antiendocrine disruptors because they suppressed bisphenol A-induced luc activities.