Downregulation of estrogen receptor alpha and beta expression in carcinogen-induced mammary gland tumors of rats.
OBJECTIVE
The recent discovery of a new isoform of estrogen receptor (ER), ER beta, has promoted the investigation of its expression on mammary gland. This study was carried out to examine the expression of ER alpha, ER beta and proliferating cell nuclear antigen (PCNA) in the carcinogen-induced mammary tumors induced by N-methyl-N-nitrosourea (MNU) or 7,12-dimethylbenz[a]anthracene (DMBA), and to compare these expression with those of age-matched normal mammary glands.


RESULTS
There was significant decrease of expression of ER alpha and ER beta in the mammary gland tumors compared with age-matched normal mammary glands (p < 0.05). In mammary gland tumors, ER alpha expression was mainly located in epithelial cells, showing intranuclear staining pattern. The decrease of ER beta expression was so distant that some tumor cells did not show any expression. There was a complete loss of ER beta expression in 50% (7/14) of MNU-induced mammary gland tumors, and 68.2% (15/22) of DMBA-induced mammary gland tumors. However, there was no difference in PCNA expression between mammary gland tumors and normal mammary glands.


CONCLUSIONS
This study represents that the decrease of expression of ER alpha and ER beta is associated with mammary carcinogenesis, and suggests that modulation of ER alpha and ER beta may be the target for the treatment of mammary gland tumors.
Kang
Jin Seok
JS
National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul 122-704, South Korea. jinskang@yahoo.com
Jung
Na Jin
NJ
Kim
Seyl
S
Kim
Dae Joong
DJ
Jang
Dong Deuk
DD
Yang
Ki-Hwa
KH
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D008770:Methylnitrosourea / Q000633:toxicity; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D018809:Proliferating Cell Nuclear Antigen; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea