| | |  | | | | Record from Web of Science® | | | | | | |
| 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 |
|
|
| Author(s): Bartholomew JS, Glenville S, Sarkar S, Burt DJ, Stanley MA, RuizCabello F, Jin CG, Garrido F, Stern PL |
| Source: CANCER RESEARCH Volume: 57 Issue: 5 Pages: 937-942 Published: MAR 1 1997 |
| Times Cited: 30 References: 48 |
| 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 medulation 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Bartholomew, JS (reprint author), CHRISTIE HOSP NHS TRUST, DEPT IMMUNOL, PATERSON INST CANC RES, WILMSLOW RD, MANCHESTER M20 4BX, LANCS ENGLAND |
Addresses:
1. UNIV CAMBRIDGE, DEPT PATHOL, CAMBRIDGE CB2 1QP, ENGLAND
2. UNIV GRANADA, SERV ANALISIS CLIN, HOSP UNIV VIRGEN NIEVES, GRANADA, SPAIN |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: WK897 |
| ISSN: 0008-5472 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |