Absence of progesterone receptor membrane component 1 reduces migration and metastasis of breast cancer

被引:17
|
作者
Lee, Sang R. [1 ]
Lee, Young Ho [1 ]
Jo, Seong Lae [1 ]
Heo, Jun H. [1 ]
Kim, Globinna [2 ]
Lee, Geun-Shik [3 ]
An, Beum-Soo [4 ]
Baek, In-Jeoung [2 ]
Hong, Eui-Ju [1 ]
机构
[1] Chungnam Natl Univ, Coll Vet Med, Suite 401,Vet Med Bldg,99 Daehak Ro, Daejeon 34134, South Korea
[2] Univ Ulsan, Dept Convergence Med, Asan Med Ctr, Coll Med, 88,Olymp Ro 43 Gil, Seoul 05505, South Korea
[3] Kangwon Natl Univ, Coll Vet Med, Chunchon 24341, South Korea
[4] Pusan Natl Univ, Dept Biomat Sci, Miryang 50463, South Korea
基金
新加坡国家研究基金会;
关键词
Pgrmc1; Breast cancer; Lung; Metastasis; Migration; DE-NOVO; PGRMC1; EXPRESSION; CELLS; ACTIVATION; SURVIVAL; PROTEIN; RISK;
D O I
10.1186/s12964-021-00719-w
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background Progesterone receptor membrane component 1 (Pgrmc1) is a non-classical progesterone receptor associated with the development of the mammary gland and xenograft-induced breast cancer. Importantly, Pgrmc1 is associated with the expression of estrogen receptor alpha and can be used for predicting the prognosis of breast cancer. Whether the genetic deletion of Pgrmc1 affects the progression of breast cancer is still unclear. Methods We used MMTV-PyMT transgenic mice that spontaneously develop breast tumors. In backcrossed FVB Pgrmc1 knockout (KO) mice, we monitored the development of the primary tumor and lung metastasis. In MCF-7 and MDA-MB-231 tumor cell lines, the migratory activity was evaluated after Pgrmc1 knockdown. Results There was no significant difference in the development of breast cancer in terms of tumor size at 13 weeks of age between WT and Pgrmc1 KO mice. However, Pgrmc1 KO mice had a significantly longer survival duration compared with WT mice. Furthermore, Pgrmc1 KO mice exhibited a significantly lower degree of lung metastasis. Compared with those of WT mice, the tumors of Pgrmc1 KO mice had a low expression of focal adhesion kinase and epithelial-mesenchymal transition markers. PGRMC1 knockdown resulted in a significantly reduced migration rate in breast cancer cell lines. Conclusions Pgrmc1 KO mice with breast cancer had a prolonged survival, which was accompanied by a low degree of lung metastasis. PGRMC1 showed a significant role in the migration of breast cancer cells, and may serve as a potential therapeutic target in breast cancer.
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页数:11
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