| Sex steroid hormones as well glucocorticoids exert important roles in the development andfunctions of the mammary gland. Glucocorticoids have been shown to induce differen-tiation ofmammary epithelial cells in primary culture and to be essential for the initiation and maintenanceof lactation. The responsiveness of human breast cancer cells to steroids has been extensivelyinvestigated in vitro. Thus, glucocorticoid-dependent inhibition of cell growth has beendemonstrated in different breast cancer cell lines. But the mechanism of glucocorticoid functionin the development and progression of the breast cancer and the regulation of glucocorticoid in localtissue are still not clear.By ligand-binding assays, glucocorticoid receptors (GR) have been foundto be present in about33–50%of human breast cancer. Recently, it has been shown thatactivation of glucocorticoid receptor by dexamethasone inhibited estrogen-dependent breastcancer growth in vitro and in xenograft model.In glucocorticoid target tissues, intracellularglucocorticoid levels are modulated by two11β-hydroxysteroid dehydroge-nase (11β-HSD)isoenzymes, type1and type2, which catalyze the interconversion of glucocorticoids from theirinactive (cortisone) to their active form (cortisol).11β-HSD type1is the isoenzyme whichconverts cortisone to cortisol while17β-HSD type2converts cortisol into cortisone in severaltissues. Gene deletion experi ments in mice suggest that the role of17β-HSD type2is both tomaintain circulating glucocorticoid levels and to provide higher local concentration ofglucocorticoids in the liver. On the other hand, inhibition of the activity of11β-HSD type2, theisoform which converts cortisol to the inactive steroid cortisone, has been shown to enhance theantiproliferative effect of glucocorticoids. The report has recently identified11β-HSD type1from a genome-wide linkage analysis as a possible candidate gene for breast cancer risk inpostmenopausal women.To better understand the role of11β-HSD type1and glucocorticoid receptors in breastcancer development and/or evolution, we prepare the protein of11β-HSD type1and thepeptide sequence located at amino acid position42–225of the human11β-HSD type1. Weinjected sc with1ml at multiple sites of four New-Zealand rabbits. Collect the antiserum of the rabbits and purify it. Positive antiserum was analyzed by immunoblot. The expression of11β-HSD1and CDC-47,ERα,PRB,GR in84specimens of female human breast carcinomaand adjacent non-malignant tissues were studied by immunocytochemistry. We located theenzymes and glucocorticoid receptors in breast cancer tissue and adjacent non-malignanttissues. These results were correlated with the clinical parameters.Results:1, Immunostaining for11β-HSD type1could be detected in the cytoplasm oftumor cells in54cases out of the84cases of breast cancer (64.3%). Usually, the cytoplasmicstaining expression appeared weak. The surrounding interstitial cells were generally devoid ofany specific staining. In non-malignant adjacent tissues, strong staining was seen in epithelialcells bordering the lumen (luminal cells) in both acini and ducts in91.7%of cases. Labeledstromal cells were occasionally observed. No staining could be detected when the antiserumimmunoabsorbed with the antigen (11β-HSD type1) or pre-immune serum was used (notshown). The expression of the enzyme was significantly lower (p <0.001) in tumors than innormal adjacent tissues.2, Steroid hormone receptors (ERα, AR, PR and GR) as well asCDC47immunoreactivity was almost exclusively found in nuclei of both cancer cells andepithelial cells from non-malignant adjacent tissues. In the84tumors examined,71.4%werepositive for ERα,78.6%for PRB and72.6%for GR. In non-malignant specimens, ERα waspositive in67.9%, PRB in64.3%and GR in95.2%of cases. The percentage of tumorsconsidered as positive for PRB was significantly higher (p <0.05) than the percentage ofpositive normal adjacent tissues. On the other hand, the percentage of tumors positive for GRwas significantly lowers (p <0.001) than that of positive normal adjacent tissues. Asexpected, the percentage of tumors considered as positive for CDC47was significantly higherthan that of non-tumoral adjacent tissues (77.4%vs.15.5%; p <0.001). No staining wasdetected when the antisera were immunoab-sorbed with the corresponding antigen (data notshown).3, Correlation between the different parameters studied: In malignant tissue, theexpression of11β-HSD1was significantly correlated with the metastasis of the axillary nodes(X2=8.192,P=0.042); the expression of11β-HSD1was significantly correlated with GR andCDC-47(r=-0.327,p=0.002; r=-0.232,p=0.033, respectively).The expression of11β-HSD1wassignificantly correlated with PRB(r=0.218,p=0.047). The expression of GR was significantlycorrelated with ERα and PRB(r=-0.262, p=0.016, r=-0.262,p=0.016, respectively). In adjacentnon-malignant tissues, the expression of11β-HSD type1was significantly correlated with PRB (r=0.269,p=0.013), the expression of PRB was significantly correlated with ERα and CDC-47(r=0.351,p=0.001, r=0.492,p=0.000, respectively).Conclusion:1, the expression of the11β-HSD type1was significantly lower in tumorsthan in normal adjacent tissues. It might be suggested that the enzyme might inhibit thepathogenesis and development of breast cancer. This is identified by the relationship between11β-HSD type1and CDC-47too.2, the percentage of tumors positive for GR wassignificantly lower than that of positive in normal adjacent tissues, it suggested GR mightplay a role in pathogenesis and development in breast cancer.3, the expression of11β-HSD1was significantly correlated with GR in breast cancer tissue. It suggested11β-HSD1may playa role through the other way independent of GR and further research is required.4, theexpression of11β-HSD type1was significantly correlated with the metastasis of the axillarylymph nodes, it suggested the enzyme may has a role in the metastasis of breast cancer andregulation of the enzyme in local tissue might be inhibit the metastasis of breast cancer. Thisgives us a new way for clinical research.5,treatment with glucocorticoid may be useful inbreast cancer patients whose expression of ER was negative or lower, this study maybeprovide a new way to treat ER-negative breast cancer.This experiment is conducted in Molecular Endocrinology and Oncology ResearchCenter of Laval University Hospital Research Center in Canada,the paper related to the topicwas published on "Pathology&Oncology Research"(SCI, Impact Factor:1.483).
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