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  • 1
    ISSN: 1432-0851
    Keywords: Key words Dexamethasone ; Breast tumour cell lines ; Major histocompatibility antigens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  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 (H2-RIIBP-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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1211
    Keywords: HLA Null allele RNA splicing Mutation Cervical cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The expression of major histocompatibility complex (MHC) class I antigens was studied in five breast carcinoma cell lines before and after treatment with 17-β estradiol. Increased HLA class I antigen expression correlated with the presence of estrogen receptors. The modulation of expression appeared to be mediated by transcriptional mechanisms, as revealed by class I mRNA levels. To elucidate the basis of MHC class I upregulation, we examined transcriptional factor binding activity to the class I regulatory element (CRE). Our results showed that 17-β estradiol induced increases in factor binding activity to the CRE II probe, and decreases to the CRE I probe. In addition, our results suggested that factors that bind the CRE I region may modulate the binding of CRE II. Binding to CRE II was significantly increased in extracts pretreated with a competitor that contained the CRE I sequence, and that bound NF-kB/kBF1. In addition, induction of NF-kB binding activity by the tumor necrosis factor was accompanied by a decrease in nuclear factors that bind to the CRE II region.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7276
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HLA class I and II expression was studied on 244 (177 primary and 67 metastatic) solid human tumours of different origin. Alkaline immunophosphatase (APAAP) and immunoperoxidase were used on cryostatic sections to stain MHC antigens. Monomorphic MoAbs were used against class I heavy chain, β2-microglobulin, DR, DQ and DP molecules. Class I expression was homogeneous on colon, melanoma and epidermoidal primitive tumours. Loss of HLA class I antigens was more frequent on basal cell carcinomas and sarcomas and was related to tumour differentiation on larynx carcinoma. Class I expression was heterogeneous on breast, larynx and stomach primitive neoplasias. Class I negative tumours were more frequent on metastatic than on primitive melanomas. Divergence of class I between primary tumours and autologous metastases was observed on melanomas, larynx and colorectal carcinomas. Class II expression was heterogeneous on all tumours and in a large number of cases was associated with high intensity of leukocytic infiltrate. HLA-DR expression was higher than HLA-DP and HLA-DQ (DR〉DP〉DQ) and was related to tumour progression. Four human tumour cell lines were modulated with recombinant interferon-γ for HLA class I and II antigens. Different HLA profiles were obtained: increased class I and II expression, increased class II or a low response. Finally, class I genes from 22 tumours were compared with autologous normal cells by Southern blot analysis: 12 tumours were class I positive and 10 negative. No clear differences in RFLP were observed that could be associated with class I rearrangement. The results are discussed in relation to the role that histocompatibility antigens may play in tumour progression and invasiveness.
    Type of Medium: Electronic Resource
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