Association of circulating Progesterone Receptor Membrane Component-1 (PGRMC1) with PGRMC1 expression in breast tumour tissue and with clinical breast tumour characteristics

Maturitas ◽  
2020 ◽  
Vol 140 ◽  
pp. 64-71
Author(s):  
Guiju Cai ◽  
Xue Yang ◽  
Xiangyan Ruan ◽  
Jing Wang ◽  
Yi Fang ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Breast Tumour ◽  
Tumour Tissue ◽  
Membrane Component ◽  
Receptor Membrane ◽  
Clinical Breast ◽  
Breast Tumour Tissue ◽  
Tumour Characteristics

scholarly journals Glycyrrhizin Derivatives Suppress Cancer Chemoresistance by Inhibiting Progesterone Receptor Membrane Component 1

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3265
Author(s):  
Yasuaki Kabe ◽  
Ikko Koike ◽  
Tatsuya Yamamoto ◽  
Miwa Hirai ◽  
Ayaka Kanai ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Cancer Progression ◽  
Egf Receptor ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Human Colon ◽  
Titration Calorimetry ◽  
Membrane Component ◽  
Human Colon Cancer ◽  
Receptor Membrane

Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in various cancer cells and contributes to tumor progression. We have previously shown that PGRMC1 forms a unique heme-stacking functional dimer to enhance EGF receptor (EGFR) activity required for cancer proliferation and chemoresistance, and the dimer dissociates by carbon monoxide to attenuate its biological actions. Here, we determined that glycyrrhizin (GL), which is conventionally used to ameliorate inflammation, specifically binds to heme-dimerized PGRMC1. Binding analyses using isothermal titration calorimetry revealed that some GL derivatives, including its glucoside-derivative (GlucoGL), bind to PGRMC1 potently, whereas its aglycone, glycyrrhetinic acid (GA), does not bind. GL and GlucoGL inhibit the interaction between PGRMC1 and EGFR, thereby suppressing EGFR-mediated signaling required for cancer progression. GL and GlucoGL significantly enhanced EGFR inhibitor erlotinib- or cisplatin (CDDP)-induced cell death in human colon cancer HCT116 cells. In addition, GL derivatives suppressed the intracellular uptake of low-density lipoprotein (LDL) by inhibiting the interaction between PGRMC1 and the LDL receptor (LDLR). Effects on other pathways cannot be excluded. Treatment with GlucoGL and CDDP significantly suppressed tumor growth following xenograft transplantation in mice. Collectively, this study indicates that GL derivatives are novel inhibitors of PGRMC1 that suppress cancer progression, and our findings provide new insights for cancer treatment.

Progesterone receptor membrane component 1 (PGRMC1) expression in canine mammary tumors: A preliminary study

2020 ◽  
Vol 132 ◽  
pp. 101-107
Author(s):  
Laura Terzaghi ◽  
Barbara Banco ◽  
Debora Groppetti ◽  
Priscila C. Dall'Acqua ◽  
Chiara Giudice ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Mammary Tumors ◽  
Membrane Component ◽  
Canine Mammary Tumors ◽  
Receptor Membrane ◽  
Preliminary Study

scholarly journals Progesterone receptor membrane component 1 reduces cardiac steatosis and lipotoxicity via activation of fatty acid oxidation and mitochondrial respiration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang R. Lee ◽  
Jun H. Heo ◽  
Seong Lae Jo ◽  
Globinna Kim ◽  
Su Jung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Membrane Component ◽  
Markers Of Inflammation ◽  
Receptor Membrane

AbstractObesity is implicated in cardiovascular disease and heart failure. When fatty acids are transported to and not adequately oxidized in cardiac cells, they accumulate, causing lipotoxicity in the heart. Since hepatic progesterone receptor membrane component 1 (Pgrmc1) suppressed de novo lipogenesis in a previous study, it was questioned whether cardiac Pgrmc1 protects against lipotoxicity. Hence, we focused on the role of cardiac Pgrmc1 in basal (Resting), glucose-dominant (Refed) and lipid-dominant high-fat diet (HFD) conditions. Pgrmc1 KO mice showed high FFA levels and low glucose levels compared to wild-type (WT) mice. Pgrmc1 KO mice presented low number of mitochondrial DNA copies in heart, and it was concomitantly observed with low expression of TCA cycle genes and oxidative phosphorylation genes. Pgrmc1 absence in heart presented low fatty acid oxidation activity in all conditions, but the production of acetyl-CoA and ATP was in pronounced suppression only in HFD condition. Furthermore, HFD Pgrmc1 KO mice resulted in high cardiac fatty acyl-CoA levels and TG level. Accordingly, HFD Pgrmc1 KO mice were prone to cardiac lipotoxicity, featuring high levels in markers of inflammation, endoplasmic reticulum stress, oxidative stress, fibrosis, and heart failure. In vitro study, it was also confirmed that Pgrmc1 enhances rates of mitochondrial respiration and fatty acid oxidation. This study is clinically important because mitochondrial defects in Pgrmc1 KO mice hearts represent the late phase of cardiac failure.

scholarly journals Roles of Progesterone Receptor Membrane Component 1 in Oxidative Stress–Induced Aging in Chorion Cells

2018 ◽  
Vol 26 (3) ◽  
pp. 394-403 ◽  
Author(s):  
Liping Feng ◽  
Terrence K. Allen ◽  
William P. Marinello ◽  
Amy P. Murtha
Keyword(s):  
Oxidative Stress ◽  
Progesterone Receptor ◽  
Membrane Component ◽  
Receptor Membrane

Progesterone receptor membrane component 1 is required for mammary gland development†

2020 ◽  
Vol 103 (6) ◽  
pp. 1249-1259
Author(s):  
Globinna Kim ◽  
Jong Geol Lee ◽  
Seung-A Cheong ◽  
Jung-Min Yon ◽  
Myeong Sup Lee ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Progesterone Receptor ◽  
Mammary Gland Development ◽  
Target Genes ◽  
Hormone Treatment ◽  
Mammary Glands ◽  
Membrane Component ◽  
Independent Manner ◽  
Receptor Membrane ◽  
Gland Development

Abstract The physiological functions of progesterone (P4) in female reproductive organs including the mammary glands are mediated via the progesterone receptor (PR), but not all P4 functions can be explained by PR-mediated signaling. Progesterone receptor membrane component 1 (PGRMC1), a potential mediator of P4 actions, plays an important role in the ovary and uterus in maintaining female fertility and pregnancy, but its function in mammary glands has not been elucidated. This study investigated the role of PGRMC1 in mouse mammary gland development. Unlike in the uterus, exogenous estrogen (E2) and/or P4 did not alter PGRMC1 expression in the mammary gland, and Pgrmc1-knockout (KO) mice displayed reduced ductal elongation and side branching in response to hormone treatment. During pregnancy, PGRMC1 was expressed within both the luminal and basal epithelium and gradually increased with gestation and decreased rapidly after parturition. Moreover, although lactogenic capacity was normal after parturition, Pgrmc1 KO resulted in defective mammary gland development from puberty until midpregnancy, while the expression of PR and its target genes was not significantly different between wild-type and Pgrmc1-KO mammary gland. These data suggest that PGRMC1 is essential for mammary gland development during puberty and pregnancy in a PR-independent manner.

Sign in / Sign up

Export Citation Format

Share Document