Effect of the aromatase inhibitor vorozole on estrogen and progesterone receptor content of rat mammary carcinomas induced by 1-methyl-1-nitrosourea

Vorozole, a nonsteroidal aromatase inhibitor, impedes the post-initiation stage of chemically induced mammary carcinogenesis. While various aspects of vorozole's effects on mammary carcinoma development have been investigated, little attention has been directed to determining the estrogen recep...

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Published in:Breast cancer research and treatment 2001-12, Vol.70 (3), p.171-183
Main Authors: KNOTT, Katrina K, MCGINLEY, John N, LUBET, Ronald A, STEELE, Vernon E, THOMPSON, Henry J
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - therapeutic use
Aromatase Inhibitors
Biological and medical sciences
Breast cancer
Cancer research
Cancer therapies
Cell Division - drug effects
Chemotherapy
Diet
Drug Administration Schedule
Epithelial Cells - pathology
Female
Immunoenzyme Techniques
Mammary Neoplasms, Experimental - drug therapy
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - pathology
Medical sciences
Methylnitrosourea
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
Triazoles - therapeutic use
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Summary:Vorozole, a nonsteroidal aromatase inhibitor, impedes the post-initiation stage of chemically induced mammary carcinogenesis. While various aspects of vorozole's effects on mammary carcinoma development have been investigated, little attention has been directed to determining the estrogen receptor (ER) and progesterone receptor (PR) content of mammary carcinomas that arise despite vorozole treatment. Female Sprague-Dawley rats were given an i.p. injection of 50mg MNU/kg body weight at 21 days of age and placed on diet supplemented with 0 or 3 mg vorozole/kg, which had no effect on mammary tumor development. Histologically confirmed carcinomas were evaluated for ER and PR by immunohistochemistry. In the control group, 78.8% of carcinomas were ER positive with an ER content ranging from 13.8 to 40.0%, similar to ER content of mammary ductal epithelial cells from non-carcinogen treated animals. PR content ranged from 4.4 to 45.2% and also was similar to levels of PR observed in ductal epithelial cells. ER was not correlated with PR in mammary carcinomas (r = 0.05, p > 0.80), whereas there was a significant correlation in ductal epithelium (r = 0.86, p = 0.006). In vorozole-treated rats, no ER negative carcinomas were observed and overall ER expression by vorozole was elevated (p < 0.03). All carcinomas from vorozole-treated rats expressed PR (2.5-60.2%) and correlation between ER and PR content was numerically greater in carcinomas from vorozole-treated animals (r = 0.42, p = 0.09). These data, which are considered hypothesis generating, provide evidence that low doses of vorozole in the diet select for mammary carcinomas with an increased ER positive phenotype.
ISSN:0167-6806
1573-7217
DOI:10.1023/a:1013051107535