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

Sang R Lee,Beum-Soo An,Young Ho Lee,Eui-Ju Hong,Globinna Kim,Jun H Heo,In-Jeoung Baek,Geun-Shik Lee,Seong Lae Jo

doi:10.1186/s12964-021-00719-w

Abstract

BackgroundProgesterone 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.MethodsWe 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.ResultsThere 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.ConclusionsPgrmc1 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.AYstNrTAYcCJz1LVvudn4eVideo

Highlights

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
The PyMT model cannot represent all types of breast cancer, our results are meaningful because lung metastasis in breast cancer is associated with high mortality; the suppression of PGRMC1 should be highlighted as a potential therapeutic strategy for increasing the life expectancy and survival rate of patients with breast cancer
In a previous study using xenograft models, PGRMC1 depletion in MCF7 and T47D cells resulted in suppression of tumor growth [12]; as both MCF7 and T47D cells belong to the luminal A subtype, PGRMC1 was suggested to regulate the growth of breast cancer via ER signaling [12]

Summary

Introduction

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. Another study reported that Pgrmc is involved in mTOR activation and EGFR signaling [13] These findings suggest that Pgrmc is closely involved in the development of breast cancer; an in vivo study using genetic deletion of Pgrmc has yet to be conducted. It is still unclear whether metastasis of breast cancers can be influenced by the levels of PGRMC1 protein. The progression and metastasis of breast cancer should be evaluated in genetically engineered mice such as MMTVPyMT [14], which were useful in investigating the role of adhesion proteins in breast cancer metastasis [15]

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