[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].

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.