ABSTRACT
We studied the content and expression of mRNA for estrogen receptors-alpha and -beta in breast tumors before and after 3-month neoadjuvant hormone therapy with antiestrogen tamoxifen and/or aromatase inhibitors. Expression of estrogen receptors-alpha and -beta was most often detected in ER+PR+ tumors and most significantly decreased in these neoplasms after exemestane therapy. Immunocytochemical and radioligand assays showed that tamoxifen and anastrozole have little effect on the number of estrogen receptors-alpha. The number of progesterone receptors in tumors decreased by the end of anastrozole therapy. Estrogen receptors-beta were immunocytochemically revealed in 50% primary breast tumors. Anastrozole slightly decreased, while tamoxifen increased the incidence of these receptors. Interruption of signaling through estrogen receptors and suppression of estrogen biosynthesis had different effects on the receptor status of neoplasms and distribution of estrogen receptors-alpha and -beta.
Subject(s)
Breast Neoplasms/genetics , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Gene Expression Regulation, Neoplastic/drug effects , Anastrozole , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Estrogen Receptor Modulators/therapeutic use , Estrogen Receptor alpha/drug effects , Estrogen Receptor beta/drug effects , Female , Humans , Nitriles/administration & dosage , Nitriles/therapeutic use , RNA, Messenger/genetics , Receptors, Progesterone/drug effects , Receptors, Progesterone/genetics , Tamoxifen/administration & dosage , Tamoxifen/therapeutic use , Triazoles/administration & dosage , Triazoles/therapeutic useABSTRACT
Expression of estrogen receptors alpha and beta was studied by the PCR method in 22 primary receptor-positive or receptor-negative breast carcinomas obtained during surgical intervention from patients aged 41-77 years and activity of aromatase in the same specimens was evaluated by the formation of tritiated water from labeled androgen precursor. Expression of estrogen receptors alpha and beta was more often detected in receptor-positive tumors characterized by lower aromatase activity. The authors conclude that the intensity of local production of estrogens can be one of the regulators of their expression, limiting this expression in case of more active production of estrogen in the tumor. On the other hand, there were no differences in the expression of estrogen beta-receptor gene or in detection of this receptor by immunocytochemical method in primary tumors lacking one of these receptors, and hence, this form of estrogen receptors is less involved in induction of progesterone receptors than alpha-receptors.
