Carcinogenesis, Vol 19, 471-477, Copyright © 1998 by Oxford University Press
JJ Li, X Hou, J Bentel, EM Yazlovitskaya and SA Li
Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for
human breast and hepatic cancer which parallel in some respects its effects
on estrogen-induced neoplasms in the hamster kidney and liver. EE has been
shown to be only weakly carcinogenic in the hamster kidney, but the most
potent carcinogenic estrogen in the hamster liver following prolonged
treatment. Unexpectedly, when EE and potent carcinogenic estrogens, such as
diethylstilbestrol (DES), 17beta- estradiol (E2) and Moxestrol (MOX), are
administered concomitantly, estrogen-induced carcinogenesis in the kidney
is completely prevented. In studying this novel finding, we found that,
compared with E2 exposure alone, EE at 0.05 and 1.0 nM significantly (P
< 0.001) inhibited the rise in proliferation of cultured primary hamster
proximal renal tubular (PRT) cells in the presence of E2 (1.0 nM).
Consistent with these findings, combined EE + DES treatment for 5.0 months
reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and
52%, respectively, compared with levels observed after DES treatment alone.
Interestingly, TAM + DES treatment for the same period also resulted in the
same low level of RNA expression of these proto- oncogenes. c-MYC, c-FOS
and c-JUN protein products were comparably reduced after either EE + DES or
TAM + DES treatment. It appears that c- fos expression and c-FOS protein
levels in the hamster kidney were more responsive to TAM inhibition. These
data demonstrate that EE possesses unique anti-tumorigenic properties in
vivo in the hamster kidney. Additionally, the observed anti-estrogen-like
effect of EE on cell proliferation of cultured PRT cells suggests that EE
may interfere critically with estrogen receptor (ER)-mediated mitogenic
pathway(s) affected by potent carcinogenic estrogens, thus preventing
subsequent gene dysregulation and, hence, tumor development. Based on
competition studies, the differential binding of EE to hamster kidney ER
relative to that of the other estrogens (E2, DES, MOX) appears not to
contribute to the prevention of estrogen carcinogenesis at this organ site
by EE.
ARTICLES
Prevention of estrogen carcinogenesis in the hamster kidney by ethinylestradiol: some unique properties of a synthetic estrogen
Kansas Cancer Institute, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66160- 7312, USA. jli1@kumc.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. H. Fowke, X.-O. Shu, Q. Dai, F. Jin, Q. Cai, Y.-T. Gao, and W. Zheng Oral Contraceptive Use and Breast Cancer Risk: Modification by NAD(P)H:Quinone Oxoreductase (NQO1) Genetic Polymorphisms Cancer Epidemiol. Biomarkers Prev., August 1, 2004; 13(8): 1308 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sasaki, M. Kaneuchi, N. Sakuragi, and R. Dahiya Multiple Promoters of Catechol-O-methyltransferase Gene Are Selectively Inactivated by CpG Hypermethylation in Endometrial Cancer Cancer Res., June 15, 2003; 63(12): 3101 - 3106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Li, S. J. Weroha, M. F. Davis, O. Tawfik, X. Hou, and S. A. Li ER and PR in Renomedullary Interstitial Cells During Syrian Hamster Estrogen-Induced Tumorigenesis: Evidence for Receptor-Mediated Oncogenesis Endocrinology, September 1, 2001; 142(9): 4006 - 4014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Hyder, C. Chiappetta, and G. M. Stancel Synthetic Estrogen 17alpha -Ethinyl Estradiol Induces Pattern of Uterine Gene Expression Similar to Endogenous Estrogen 17beta -Estradiol J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 740 - 747. [Abstract] [Full Text]
|
|