Estrogen signaling in colorectal carcinoma microenvironment: expression of ERβ1, AIB-1, and TIF-2 is upregulated in cancer-associated myofibroblasts and correlates with disease progression
| Autor: | Haralabos P. Kalofonos, Zinovia Kefalopoulou, Georgia Sotiropoulou-Bonikou, John Varakis, Vassiliki Tzelepi, Petros Grivas, Maria Melachrinou |
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| Rok vydání: | 2009 |
| Předmět: |
Adenoma
Adult Male Pathology medicine.medical_specialty Stromal cell medicine.drug_class Myocytes Smooth Muscle Gene Expression Estrogen receptor Kaplan-Meier Estimate Biology Pathology and Forensic Medicine Nuclear Receptor Coactivator 3 Nuclear Receptor Coactivator 2 Biomarkers Tumor medicine Estrogen Receptor beta Humans Molecular Biology Estrogen receptor beta Aged Histone Acetyltransferases Neoplasm Staging Aged 80 and over Carcinoma Cancer Estrogens Cell Biology General Medicine Fibroblasts Middle Aged medicine.disease Immunohistochemistry Up-Regulation Cell Transformation Neoplastic Estrogen Nuclear receptor coactivator 3 Disease Progression Trans-Activators Female Signal transduction Colorectal Neoplasms Signal Transduction |
| Zdroj: | Virchows Archiv. 454:389-399 |
| ISSN: | 1432-2307 0945-6317 |
| Popis: | Epidemiological and molecular data suggest the involvement of estrogen signaling in colorectal tissue, mediated mainly through estrogen receptor beta (ERbeta). Estrogens may mediate their effects in epithelial cells indirectly by acting on stromal cells. Expression of ERalpha, ERbeta1, and the ER coregulators, amplified in breast cancer-1 (AIB-1) and transcriptional intermediary factor 2 (TIF-2), was evaluated in myofibroblasts of 107 colorectal carcinomas, 77 paired samples of normal mucosa, and 29 adenomas by immunohistochemistry. Double immunostaining with a-SMA was used to identify the myofibroblasts of normal tissue, adenomas, and cancer microenvironment. ERalpha was not expressed in stromal cells. Nuclear expression of ERbeta1, AIB-1, and TIF-2 in myofibroblasts gradually increased from normal mucosa, through adenomas, to carcinomas. Cytoplasmic ERbeta1 and TIF-2 expression was enhanced in carcinomas compared to normal mucosa and adenomas. Enhanced nuclear and cytoplasmic ERbeta1 expression and elevated nuclear AIB-1 expression were more frequently noted in myofibroblasts of carcinomas of advanced stage. ERbeta1 expression in cancer-associated myofibroblasts correlated to AIB-1 and TIF-2 expression. None of the markers correlated with patients' prognosis. Our findings imply that ERbeta1-dependent (genomic and non-genomic) and ER-coregulator-dependent (AIB-1, TIF-2) signal transductions in myofibroblasts may be involved in the initiation and progression of colorectal carcinomas. |
| Databáze: | OpenAIRE |
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