Related Experiment Video

Updated: Dec 5, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.9K

PGRMC1 Inhibits Progesterone-Evoked Proliferation and Ca2+ Entry Via STIM2 in MDA-MB-231 Cells

Carlos Cantonero1, Ginés M Salido1, Juan A Rosado1

  • 1Department of Physiology (PHYCELL Group) of Veterinary Faculty and Institute of Molecular Pathology Biomarkers (IMPB) of University of Extremadura, 10003 Caceres, Spain.

International Journal of Molecular Sciences
|October 20, 2020
PubMed

Insights

Progesterone (P4) triggers calcium (Ca2+) changes in breast cancer cells via a new pathway involving STIM2, Orai1, and TRPC1. Progesterone receptor membrane component 1 (PGRMC1) downregulates this pathway, impacting cell proliferation and death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Progesterone receptor membrane component 1 (PGRMC1) influences cancer hallmarks.
  • Progesterone (P4) induces intracellular calcium (Ca2+) changes in various breast cancer cell lines, including triple-negative (MDA-MB-231) and luminal (MCF7) types.
  • PGRMC1 expression is elevated in certain cancer cells, and its silencing can affect P4-evoked Ca2+ mobilization.

Purpose of the Study:

  • To identify novel P4-dependent Ca2+ mobilization pathways in triple-negative breast cancer cells (MDA-MB-231) and MCF7 cells.
  • To investigate the role of PGRMC1 in regulating this newly identified P4-evoked Ca2+ pathway.

Main Methods:

  • Investigated P4-evoked Ca2+ changes in MDA-MB-231 and MCF7 cells.
  • Utilized siRNA to silence Stromal interaction molecule 1 (STIM1) to assess its involvement.
  • Examined the effects of PGRMC1 silencing on P4-induced cell proliferation, cell death, and Nuclear Factor of Activated T-Cells 1 (NFAT1) nuclear accumulation.

Main Results:

  • A novel P4-dependent Ca2+ entry pathway involving Stromal interaction molecule 2 (STIM2), Calcium release-activated calcium channel protein 1 (Orai1), and Transient Receptor Potential Channel 1 (TRPC1) was identified.
  • Stromal interaction molecule 1 (STIM1) was found not to be involved in this pathway.
  • PGRMC1 silencing reduced the negative impact of P4 on cell proliferation and cell death in MDA-MB-231 cells, and enhanced P4-induced NFAT1 nuclear accumulation.

Conclusions:

  • These findings reveal a new P4-evoked Ca2+ entry pathway in breast cancer cells.
  • PGRMC1 plays a regulatory role in this pathway, downregulating P4-induced Ca2+ entry.
  • The modulation of this pathway by PGRMC1 affects key cellular processes like proliferation and apoptosis.
Keywords:
Ca2+-homeostasisMDA-MB-231 cellsPGRMC1STIM2progesterone

More Related Videos

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

12.5K
Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

10.3K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
37.7K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
9.8K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.5K