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    Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in cervical tumor cells.

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    Authors
    Bartholomew, Jennifer S
    Glenville, Suzanne
    Sarkar, S
    Burt, Deborah J
    Stanley, M A
    Ruiz-Cabello, F
    Chengang, Jing
    Garrido, F
    Stern, Peter L
    Affiliation
    Department of Immunology, Paterson Institute for Cancer Research, Christie Hospital, National Health Service Trust, United Kingdom.
    Issue Date
    1997-03-01
    
    Metadata
    Show full item record
    Abstract
    A crucial event in the malignant progression of cervical intraepithelial neoplasia appears to be the up-regulation of high-risk human papillomavirus (HPV) early gene expression. Steroid hormones have been linked to the progression from premalignant to neoplastic status in HPV positive lesions. This report demonstrates that at physiological levels, the glucocorticoid hormone hydrocortisone consistently down-regulates class I human leukocyte antigen (HLA) surface expression in HPV-positive cervical tumor cells but can up-regulate expression in HPV-negative epithelial tumor lines. Suppression of HLA expression was also seen with progesterone, another steroid hormone. The hydrocortisone-mediated modulation of HLA expression is dependent on integration and transcription of the HPV genome and can be blocked by Ru38486, an antagonist of both glucocorticoid and progesterone receptors, indicating the role of these receptors in mediating HLA suppression. The data suggest that HPV integration events in cervical epithelia correlate with hormone-dependent HLA suppression, possibly contributing to the avoidance of tumor recognition by cytotoxic T cells. These studies imply that clinical use of steroids may be contraindicated in HPV-positive individuals who have early premalignant cervical disease or neoplasia but provide evidence that the antiprogestin Ru38486 may be useful in the management of early stage cervical disease.
    Citation
    Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in cervical tumor cells. 1997, 57 (5):937-42 Cancer Res.
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/95184
    PubMed ID
    9041198
    Type
    Article
    Language
    en
    ISSN
    0008-5472
    Collections
    All Paterson Institute for Cancer Research

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