PMID- 9041198
OWN - NLM
STAT- MEDLINE
DCOM- 19970328
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 5
DP  - 1997 Mar 1
TI  - 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.
PG  - 937-42
AB  - 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.
FAU - Bartholomew, J S
AU  - Bartholomew JS
AD  - Department of Immunology, Paterson Institute for Cancer Research, Christie 
      Hospital, National Health Service Trust, United Kingdom.
FAU - Glenville, S
AU  - Glenville S
FAU - Sarkar, S
AU  - Sarkar S
FAU - Burt, D J
AU  - Burt DJ
FAU - Stanley, M A
AU  - Stanley MA
FAU - Ruiz-Cabello, F
AU  - Ruiz-Cabello F
FAU - Chengang, J
AU  - Chengang J
FAU - Garrido, F
AU  - Garrido F
FAU - Stern, P L
AU  - Stern PL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA, Viral)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Hormone Antagonists)
RN  - 320T6RNW1F (Mifepristone)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Carcinoma/*immunology/pathology
MH  - DNA, Viral/metabolism
MH  - Down-Regulation
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Expression Regulation, Viral/drug effects
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Hormone Antagonists/pharmacology
MH  - Humans
MH  - Hydrocortisone/*pharmacology
MH  - Mifepristone/pharmacology
MH  - Papillomaviridae/*genetics
MH  - Progesterone/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Uterine Cervical Neoplasms/genetics/*immunology/*virology
MH  - *Virus Integration
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Mar 1;57(5):937-42.