Possible role of PGRMC1 in breast cancer development

  title={Possible role of PGRMC1 in breast cancer development},
  author={Hans J Neubauer and Qianqian Ma and J. Zhou and Qian Yu and Xiangyan Ruan and Harald Seeger and Tanja N. Fehm and Alfred Otto Mueck},
  pages={509 - 513}
Abstract Hormone therapy may increase the risk of breast cancer. Thus, especially the addition of synthetic progestins may play a decisive role according to the results of clinical studies. Overexpression of a special receptor, i.e. the progesterone receptor membrane component-1 (PGRMC1), may offer a potential new pathway to explain the observed increase in breast cancer risk in the combined arm of the Women's Health Initiative. PGRMC1 is expressed in breast cancer tissue and may be important… 

PGRMC1 Promotes Progestin-Dependent Proliferation of Breast Cancer Cells by Binding Prohibitins Resulting in Activation of ERα Signaling

Strong evidence is provided that activated PGRMC1 associates with PHBs, competitively removing them from ERα, which then can develop its transcriptional activities on target genes, which may provide a new avenue to target hormone-dependent breast cancer.

May progesterone receptor membrane component 1 (PGRMC1) predict the risk of breast cancer?

  • Ying ZhangX. Ruan A. Mueck
  • Medicine, Biology
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2016
It can be suggested that women with breast epithelium highly expressing PGRMC1 and in interaction with ERα may have an increased risk to develop breast cancer, especially when treated with hormone therapy.

High Level of Progesteron Receptor Membrane Component 1 (PGRMC 1) in Tissue of Breast Cancer Patients is Associated with Worse Response to Anthracycline-Based Neoadjuvant Therapy.

It is demonstrated that PGRMC1 might play an important role in progression and therapy resistance of human breast tumors and could offer an interesting target for anticancer therapy.

PGRMC1 in animal breast cancer tissue and blood is associated with increased tumor growth with norethisterone in contrast to progesterone and dydrogesterone: four-arm randomized placebo-controlled xenograft study

An animal model was used to compare tumor growth using progesterone and its isomer dydrogesterone with norethisterone, which elicited in in vitro studies the strongest proliferating effect.

Progesterone receptor membrane component 1 promotes the growth of breast cancers by altering the phosphoproteome and augmenting EGFR/PI3K/AKT signalling

It is demonstrated that PGRMC1 plays a prominent role in regulating the growth of cancer cells by altering the PI3K/AKT/mTOR and EGFR signalling mechanisms in both ER-positive and TNBC cells.

Identification of PGRMC1 as a Candidate Oncogene for Head and Neck Cancers and Its Involvement in Metabolic Activities

  • Yue ZhaoX. Ruan
  • Medicine, Biology
    Frontiers in Bioengineering and Biotechnology
  • 2019
In this work, the transcriptomics, genomics, and clinical data of 498 head-neck squamous cell carcinoma samples from the public-accessible database, The Cancer Genome Atlas, demonstrated that PGRMC1 expression served as a predictor for worse OS and the over-expression of P GRMC1 was strongly correlated with various metabolic process activity as well as cancer metastasis and cell proliferation features in human head- neck squamouscell carcinoma patient's cohort.



Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells

Some synthetic progestins trigger a proliferative response of PGRMC1-overexpressed MCF-7 cancer cells, and the effect of progestogens on breast cancer tumorigenesis may clearly depend on the specific pharmacology of the various synthetic progESTins.

The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells

Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol, and the effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.

Overexpression of progesterone receptor membrane component 1: possible mechanism for increased breast cancer risk with norethisterone in hormone therapy

The results suggest that undetected tumor cells overexpressing PGRMC1 may be more likely to develop into frank tumor cells in women undergoing E2/NET hormone therapy.

Membrane-initiated effects of progesterone on proliferation and activation of VEGF in breast cancer cells

  • H. NeubauerG. Adam T. Fehm
  • Biology, Medicine
    Climacteric : the journal of the International Menopause Society
  • 2009
PGRMC1 is expressed in breast cancer tissue and mediates an RU-486-independent proliferative signal, which might also contribute to VEGF-induced neovascularization in tumor tissue.

Elevated progesterone receptor membrane component 1/sigma‐2 receptor levels in lung tumors and plasma from lung cancer patients

Levels in clinical tumor samples from squamous cell lung cancers and lung adenocarcinomas compared to corresponding nonmalignant tissue demonstrate that Pgrmc1 is a potential tumor and serum biomarker, as well as a therapeutic target, for lung cancer.

Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1

PGRMC1 phosphorylation may be involved in the clinical differences that underpin breast tumors of differing ER status, suggesting an altered keratin pool, and increased inflammation and wound responses in estrogen receptor negative tumors.

Progestin-dependent progression of human breast tumor xenografts: a novel model for evaluating antitumor therapeutics.

This study shows that xenografts obtained from BT-474 and T47-D human breast cancer cells without Matrigel in estrogen-supplemented nude mice begin to regress within days after tumor cell inoculation, but their growth is resumed if animals are supplemented with progesterone, suggesting a possible model system for screening potential therapeutic agents for their ability to prevent or inhibit progestin-dependent human breast tumors.

Correction: Breast cancer proteomics reveals correlation between estrogen receptor status and differential phosphorylation of PGRMC1

Proteins significantly differentially abundant between estrogen receptor negative and estrogen receptor positive tumors at the 0.1% level were consistent with published profiles, suggesting an

Overexpression of the Cytochrome P450 Activator Hpr6 (Heme-1 Domain Protein/Human Progesterone Receptor) in Tumors

Hpr6 homologues regulate cytochrome P450 proteins implicated in hormone, steroid and xenobiotic chemical metabolism, suggesting that Hpr6 is an important marker for cancer progression and a potential anticancer therapeutic target.