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Experimental study on the effect of progesterone receptor membrane component 1 on hormone-induced breast cancer proliferation |
ZHAO Yue CHENG Jiaojiao |
Department of Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China |
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Abstract Objective To investigate the effect of progesterone receptor membrane component 1 (PGRMC1) on hormone-induced breast cancer proliferation. Methods On the basis of in vitro studies, 36 BALB/c-nu female nude mice were selected and divided into the stable expression of PGRMC1 (T47D/HA-PGRMC1) group and the empty vector expression (T47D/HA-Vector) group according to the random number table method, with 18 mice in each group. All nude mice were inoculated with estradiol (E2) pellets 24 hours before the injection of tumor cells into both flanks. Then the two groups were inoculated with 150 μL of DMEM-F12 containing T47D/HA-PGRMC1和T47D/HA-Vector, respectively. When the mean tumor volume reached approximately 100 mm3, the two groups were divided into three subgroups, with 6 mice of each subgroups, including subcutaneous embedding sustained-release tablets of placebo (E2+placebo subgroup), norethinne (NET) (E2+NET subgroup) and progesterone (E2+progesterone subgroup). Tumor volumes were monitored for 45 d. Tumor tissue was analyzed by immunohistochemical staining for PGRMC1 and Ki-67 at the end of treatment. Results Compared with the T47D/HA-Vector group, tumor volumes in the T47D/HA-PGRMC1 group increased by 36%. In the T47D/HA-PGRMC1 group, compared with E2+placebo subgroup, E2+NET subgroup significantly promoted tumor growth, the difference was highly statistically significant (P < 0.01). There was no significant difference between E2+progesterone subgroup and E2+placebo subgroup (P > 0.05). In the T47D/HA-Vector group, there were no statistically significant differences between E2+placebo subgroup, E2+NET subgroup and E2+progesterone subgroup (all P > 0.05). In T47D/HA-PGRMC1 group, E2+NET subgroup showed positive expression of Ki-67. The comparison of expression levels of PGRMC1 and Ki-67 among 3 subgroups showed highly statistical significance (P < 0.01). The expressions of PGRMC1 and Ki-67 in E2+NET subgroup were significantly higher than those in E2+placebo subgroup and E2+progesterone subgroup, and the differences were statistically significant (all P < 0.05). There was no significant difference in the expression levels of PGRMC1 and Ki-67 between E2+placebo subgroup and E2+progesterone subgroup (all P > 0.05). There were no significant differences in the expression of PGRMC1 and Ki-67 among 3 subgroups of the T47D/HA-Vector group (all P > 0.05). Immunohistochemical results showed that PGRMC1 was positively correlated with Ki-67 expression (r = 0.839, P = 0.002). Conclusion It is the first found that E2+NET increases the tumor growth of human breast cancer cells that overexpress PGRMC1 but not with progesterone in vivo. The results are consistent with those of in vitro experiments.
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