Dexamethasone induces altered binding of regulatory factors to HLA class I enhancer sequence in MCF-7 breast tumour cell line.
Several reports have shown the importance of MHC class I antigens in enabling the host to regulate tumour growth in vivo. Glucocorticoid hormones have strong immunosuppressive effects and are known regulators of gene transcription. In this work we studied the expression of major histocompatibility complex (MHC) class I antigens in three breast carcinoma cell lines before and after treatment with the synthetic glucocorticoid dexamethasone. HLA class I expression in the cell line MCF-7 was down-regulated in the presence of dexamethasone. This down-modulation of expression appeared to be mediated by transcriptional mechanisms, as revealed by HLA class I mRNA levels. To elucidate the basis of MHC class I down-regulation by dexamethasone, we examined transcriptional-factor-binding activity to the HLA class I regulatory element or enhancer A by electrophoretic-mobility-shift assays, using synthesized oligonucleotides corresponding to upstream conserved sequences of MHC class I genes. Our results showed that dexamethasone induced a different binding to the MHC class I regulatory elements in the MCF-7 cell line from that of the other cell lines included in our study. MCF-7 cells presented a strong decrease in previous factor-binding activity to the CRE II probe (H2RIIBP-like binding activity) and a new factor-binding activity was apparent. On the other hand, CRE I region showed an increase in KBF1-factor-binding activity. These results suggest that glucocorticoids down-modulate the expression of MHC class I antigens by altering the binding to the enhancer A sequence. In addition, this down-modulation may affect the regulation of tumour growth by the host's immune system.
Servicio de Análisis Clínicos, Hospital General de Motril, Granada, Spain.
F
F
Rodriguez
M
M
Redondo
F
F
Ruiz-Cabello
D001943:Breast Neoplasms / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004742:Enhancer Elements, Genetic; D005434:Flow Cytometry; D005805:Genes, MHC Class I; D005938:Glucocorticoids / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005938:Glucocorticoids; D015395:Histocompatibility Antigens Class I; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003907:Dexamethasone