Differential effects of PGRMC1-mediated different progesterones on proliferation of breast cancer

ZHAO Yue; JU Rui; XIE Dan; ZHANG Zheng; ZHU Jianguo; ZHANG E; LI Li

doi:10.3969/j.issn.1674-3806.2025.11.03

Abstract：Objective To explore the differences in effects of progesterone receptor membrane component 1(PGRMC1)in a nude mouse model with human breast cancer xenografts on the proliferation of breast cancer xenografts under the stimulation of progesterone and norethisterone(NET).Methods A human breast cancer cell line(MCF7)with stable expression of PGRMC1 was constructed.Thirty-six female BALB/c-nu nude mice were divided into MCF7/HA-PGRMC1 group(n=18)and MCF7/HA-Vector group(n=18)according to random number table method.Estradiol(E2)sustained-release tablets were subcutaneously embedded in the neck of each mouse.After subcutaneous embedding of E2 sustained-release tablets for 24 hours,MCF7/HA-PGRMC1 and MCF7/HA-Vector cell suspensions were respectively injected into the subcutaneous tissues on the left and right sides of the nude mice in the two groups at a dose of 150 μL,with a cell count of 1 × 107.When tumors grew to about 100 mm3 in size,the nude mice in the two groups were further divided into three subgroups:the E2+placebo subgroup(receiving subcutaneous embedding of E2 plus placebo)(n=6),the E2+progesterone subgroup(receiving subcutaneous embedding of E2 plus progesterone sustained-release tablets)(n=6)and the E2+NET subgroup(receiving subcutaneous embedding of E2 plus NET sustained-release tablets)(n=6).The volume changes of the tumors were recorded and tumor growth curves were plotted.After 45 days,the tumor tissues were completely excised,and immunohistochemical staining was performed to detect PGRMC1 and Ki67 expressions in the xenograft tissues.Results The MCF7/HA-PGRMC1 strain was successfully constructed.In the MCF7/HA-PGRMC1 group,there was no statistically significant difference in tumor growth between the E2+progesterone subgroup and the E2+placebo subgroup(P＞0.05),while the E2+NET subgroup showed significant tumor growth compared with the E2+placebo subgroup(P＜0.05).In the MCF7/HA-Vector group,there was no statistically significant difference in tumor growth between the E2+NET subgroup and the E2+placebo subgroup(P＞0.05)as well as between the E2+progesterone subgroup and the E2+placebo subgroup(P＞0.05).In the MCF7/HA-PGRMC1 group,Ki67 showed strong positive expression in the E2+NET subgroup,and PGRMC1 was positively correlated with Ki67 expression(r=0.892,P=0.014).Conclusion This experiment confirms that overexpression of PGRMC1 can specifically mediate the proliferation-promoting effect of NET combined with E2 on breast cancer in nude mice in vivo,while the combination with progesterone does not promote the additional proliferation.This discovery provides crucial animal experimental evidence for the selection of progesterone types in clinical hormone therapy.