Effect of progesterone on expression of ER, PR, PCNA, bcl-2, c-myc, c-fos, and EGFR in normal breast tissue implanted into nude mice

Abstract

Objective: To investigate the effect of progesterone on estrogen receptor(ER), progesterone receptor(PR), proliferating cell nuclear antigen (PCNA) , bcl-2 , c-myc, c-fos, and epidermal growth factor receptor(EGFR) expression in normal human breast tissues implanted into nude mice. Methods: A xenograft-model, pieces of normal human breast tissue implanted subcutaneously into 9-10-week-old athymic nude mice, was established.The tissue of each case was divided into 4 parts, and were transplanted into 4 nude mice.These mice were randomly divided into 4 groups, namely control group: normal saline 0.1 ml; estrogen group: estradiol benzoate 20 μg (0.1 ml, 1 mg/kg); progesterone group: 60 μg (0.1 ml, 3 mg/kg); estrogen plus progestin group: estradiol benzoate 20 μg (0.1 ml, 1 mg/kg) and progesterone (0.1 ml, 3 mg/kg) 60 μg.Treatment was given every other day, and human breast tissues were removed for experiments after treatment for 4 weeks.The implanted breast tissue were fixed and sliced.The expression of ER, PR PCNA and bcl-2 were assayed by immunohistochemical, c-myc, c-fos, and EGFR mRNAs were determined by in situ hybridization. Results: In estrogen group, and estrogen plus progestin group, the positive expression of ER was lower and PR was higher than those of the control group (P<0.05); the expression of ER and PR in progesterone group had no differences compared with the control group (P>0.05); the expression of PCNA and bcl-2 in estrogen group were higher than that of the control group (P<0.01, P<0.05), while they showed no significant difference in the other two drug groups compared with the control group (P>0.05). The expression of c-myc, c-fos and EGFR in estrogen group and estrogen plus progestin group were higher than those in control group (P<0.01). The expression of c-myc in the progesterone group was higher than that in the control group (P<0.01), and the expression of c-fos and EGFR in the estrogen and progesterone groups were not significantly different compared with those in the control group (P>0.05). Conclusions: Progesterone did not affect the proliferation and apoptosis of human normal breast tissue, but may have anti-proliferative and pro-apoptosis effects when coupled with estrogen.And it can up-regulate the expression of c-myc.