Expression of SOCS1 and SOCS3 genes is differentially regulated in breast cancer cells in response to proinflammatory cytokine and growth factor signals
| Autor: | C. E. Egwuagu, Althaf Lohani, Michele K. Evans, Andrzej R. Trzeciak, Cheng-Rong Yu, Mahdi Rm, Xuebin Liu |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Transcription Genetic Tumor suppressor gene medicine.medical_treatment Down-Regulation Breast Neoplasms Suppressor of Cytokine Signaling Proteins medicine.disease_cause Proinflammatory cytokine Suppressor of Cytokine Signaling 1 Protein Cell Line Tumor Genetics medicine Humans Gene silencing Growth Substances Molecular Biology STAT5 Regulation of gene expression biology Suicide gene Gene Expression Regulation Neoplastic Cytokine Suppressor of Cytokine Signaling 3 Protein biology.protein Cancer research Cytokines Inflammation Mediators Carcinogenesis Signal Transduction |
| Zdroj: | Oncogene. 26:1941-1948 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1209993 |
| Popis: | DNA-hypermethylation of SOCS genes in breast, ovarian, squamous cell and hepatocellular carcinoma has led to speculation that silencing of SOCS1 and SOCS3 genes might promote oncogenic transformation of epithelial tissues. To examine whether transcriptional silencing of SOCS genes is a common feature of human carcinoma, we have investigated regulation of SOCS genes expression by IFNgamma, IGF-1 and ionizing radiation, in a normal human mammary epithelial cell line (AG11134), two breast-cancer cell lines (MCF-7, HCC1937) and three prostate cancer cell lines. Compared to normal breast cells, we observe a high level constitutive expression of SOCS2, SOCS3, SOCS5, SOCS6, SOCS7, CIS and/or SOCS1 genes in the human cancer cells. In MCF-7 and HCC1937 breast-cancer cells, transcription of SOCS1 is dramatically up-regulated by IFNgamma and/or ionizing-radiation while SOCS3 is transiently down-regulated by IFNgamma and IGF-1, suggesting that SOCS genes are not silenced in these cells by the epigenetic mechanism of DNA-hypermethylation. We further show that the kinetics of SOCS1-mediated feedback inhibition of IFNgamma signaling is comparable to normal breast cells, indicating that the SOCS1 protein in breast-cancer cells is functional. We provide direct evidence that STAT3 pathways are constitutively activated in MCF-7 and HCC1937 cells and may drive the aberrant persistent activation of SOCS genes in breast-cancer cells. Our data therefore suggest that elevated expression of SOCS genes is a specific lesion of breast-cancer cells that may confer resistance to proinflammatory cytokines and trophic factors, by shutting down STAT1/STAT5 signaling that mediate essential functions in the mammary gland. |
| Databáze: | OpenAIRE |
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