TY - JOUR
T1 - Effect of glucocorticoid hormones on viral gene expression, growth, and dysplastic differentiation in HPV16-immortalized ectocervical cells
AU - Khare, Suvarnalatha
AU - Pater, Mary M.
AU - Tang, Shou Ching
AU - Pater, Alan
N1 - Funding Information:
We thank Ms. G. Jin for excellent technical assistance, Mr. E. Evelly for assistance in the histological studies, Dr. M. Pirai of the Grace General Hospital for analysis and samples of cervical tissues, and Ms. J. Petten for typing the manuscript. This work was supported in part by the National Cancer Institute of Canada, with funds from the Canadian Cancer Society, and by the Medical Research Council of Canada.
PY - 1997/5/1
Y1 - 1997/5/1
N2 - Steroid hormones are proposed to act as cofactors with human papillomaviruses (HPVs) in the etiology of cervical cancer. We and others reported that progesterone and glucocorticoid hormones induce the expression of HPV16 via three glucocorticoid response elements (GREs) in the viral regulatory region. Consensus GREs (GREcs) are useful in other systems for examining the effect of hormones after enhancing the response with mutated GREc constructs. Therefore, this study used human ectocervical cells (HEC) and HPV type 16 containing three GREcs to establish immortalized cells (HEC- 16GREc). Northern blot assays showed that the level of viral E6-E7 oncogene RNA was increased by hormones substantially more in HEC-16GREc than in wild- type HPV16-immortalized human ectocervical cells (HEC-16). The saturation density and the hormone response of the growth rate were significantly higher for HEC-16GREc and the doubling was faster in the presence of hormone than for HEC-16. Although both were nontumorigenic, only HEC-16GREc showed anchorage-independent growth, which was dependent on hormone. Also, HEC- 16GREc were more abnormal in their epithelium differentiation pattern in organotypic (raft) cultures. Furthermore, hormone-treated HEC-16GREc rafts showed more dysplastic features than hormone-treated HEC-16 rafts. These results suggest new features of the role of hormones: that enhanced expression of vital oncogenes in response to hormones apparently confers a greater risk for cervical cells containing HPV16. Further, HEC-16GREc could be ideal for studying hormone-dependent and -independent malignant trans formation.
AB - Steroid hormones are proposed to act as cofactors with human papillomaviruses (HPVs) in the etiology of cervical cancer. We and others reported that progesterone and glucocorticoid hormones induce the expression of HPV16 via three glucocorticoid response elements (GREs) in the viral regulatory region. Consensus GREs (GREcs) are useful in other systems for examining the effect of hormones after enhancing the response with mutated GREc constructs. Therefore, this study used human ectocervical cells (HEC) and HPV type 16 containing three GREcs to establish immortalized cells (HEC- 16GREc). Northern blot assays showed that the level of viral E6-E7 oncogene RNA was increased by hormones substantially more in HEC-16GREc than in wild- type HPV16-immortalized human ectocervical cells (HEC-16). The saturation density and the hormone response of the growth rate were significantly higher for HEC-16GREc and the doubling was faster in the presence of hormone than for HEC-16. Although both were nontumorigenic, only HEC-16GREc showed anchorage-independent growth, which was dependent on hormone. Also, HEC- 16GREc were more abnormal in their epithelium differentiation pattern in organotypic (raft) cultures. Furthermore, hormone-treated HEC-16GREc rafts showed more dysplastic features than hormone-treated HEC-16 rafts. These results suggest new features of the role of hormones: that enhanced expression of vital oncogenes in response to hormones apparently confers a greater risk for cervical cells containing HPV16. Further, HEC-16GREc could be ideal for studying hormone-dependent and -independent malignant trans formation.
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U2 - 10.1006/excr.1997.3529
DO - 10.1006/excr.1997.3529
M3 - Article
C2 - 9168812
AN - SCOPUS:0031149440
SN - 0014-4827
VL - 232
SP - 353
EP - 360
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -