High tumoral levels of Kiss1 and G-protein-coupled receptor 54 expression are correlated with poor prognosis of estrogen receptor-positive breast tumors

2007 ◽  
Vol 14 (3) ◽  
pp. 691-702 ◽  
Author(s):  
Didier Marot ◽  
Ivan Bieche ◽  
Chantal Aumas ◽  
Stéphanie Esselin ◽  
Céline Bouquet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
G Protein ◽  
Breast Tumors ◽  
Metastasis Suppressor ◽  
Mrna Levels ◽  
Breast Cancers ◽  
G Protein Coupled Receptor ◽  
Primary Tumors ◽  
G Protein Coupled

KiSS1 is a putative metastasis suppressor gene in melanoma and breast cancer-encoding kisspeptins, which are also described as neuroendocrine regulators of the gonadotropic axis. Negative as well as positive regulation of KiSS1 gene expression by estradiol (E2) has been reported in the hypothalamus. Estrogen receptor α (ERα level is recognized as a marker of breast cancer, raising the question of whether expression of KiSS1 and its G-protein-coupled receptor (GPR54) is down- or upregulated by estrogens in breast cancer cells. KiSS1 was found to be expressed in MDA-MB-231, MCF7, and T47D cell lines, but not in ZR75-1, L56Br, and MDA-MB-435 cells. KiSS1 mRNA levels decreased significantly in ERα-negative MDA-MB-231 cells expressing recombinant ERα. In contrast, tamoxifen (TAM) treatment of ERα-positive MCF7 and T47D cells increased KiSS1 and GPR54 levels. The clinical relevance of this negative regulation of KiSS1 and GPR54 by E2 was then studied in postmenopausal breast cancers. KiSS1 mRNA increased with the grade of the breast tumors. ERα-positive invasive primary tumors expressed sevenfold lower KiSS1 levels than ERα-negative tumors. Among ERα-positive breast tumors from postmenopausal women treated with TAM, high KiSS1 combined with high GPR54 mRNA tumoral levels was unexpectedly associated with shorter relapse-free survival (RFS) relative to tumors expressing low tumoral mRNA levels of both genes. The contradictory observation of putative metastasis inhibitor role of kisspeptins and RFS to TAM treatment suggests that evaluation of KiSS1 and its receptor tumoral mRNA levels could be new interesting markers of the tumoral resistance to anti-estrogen treatment.

scholarly journals Differential expression of G protein-coupled receptor associated sorting protein 1 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
G Protein ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
G Protein Coupled Receptor ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
G Protein Coupled

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding G protein-coupled receptor associated sorting protein 1, GPRASP1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. GPRASP1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. GPRASP1 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of GPRASP1 in primary tumors of the breast was correlated with overall survival in patients with luminal A subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. GPRASP1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals The G Protein–Coupled Receptor GPR30 Inhibits Proliferation of Estrogen Receptor–Positive Breast Cancer Cells

2010 ◽  
Vol 70 (3) ◽  
pp. 1184-1194 ◽  
Author(s):  
Eric A. Ariazi ◽  
Eugen Brailoiu ◽  
Smitha Yerrum ◽  
Heather A. Shupp ◽  
Michael J. Slifker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
G Protein ◽  
Breast Cancer Cells ◽  
G Protein Coupled Receptor ◽  
Estrogen Receptor Positive ◽  
G Protein Coupled ◽  
Positive Breast Cancer

scholarly journals Regulation of ERRα Gene Expression by Estrogen Receptor Agonists and Antagonists in SKBR3 Breast Cancer Cells: Differential Molecular Mechanisms Mediated by G Protein-Coupled Receptor GPR30/GPER-1

2010 ◽  
Vol 24 (5) ◽  
pp. 969-980 ◽  
Author(s):  
Yin Li ◽  
Lutz Birnbaumer ◽  
Christina T. Teng
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
G Protein ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
G Protein Coupled Receptor ◽  
Ici 182,780 ◽  
G Protein Coupled

Abstract In selected tissues and cell lines, 17β-estradiol (E2) regulates the expression of estrogen-related receptor α (ERRα), a member of the orphan nuclear receptor family. This effect is thought to be mediated by the estrogen receptor α (ERα). However in the ERα- and ERβ-negative SKBR3 breast cancer cell line, physiological levels of E2 also stimulate ERRα expression. Here, we explored the molecular mechanism that mediates estrogen action in ER-negative breast cancer cells. We observed that E2, the ERα agonist, as well as the ERα antagonists ICI 182,780 and tamoxifen (TAM), a selective ER modulator, stimulate the transcriptional activity of the ERRα gene and increase the production of ERRα protein in SKBR3 cells. Moreover, the ERRα downstream target genes expression and cellular proliferation are also increased. We show further that the G protein-coupled receptor GPR30/GPER-1 (GPER-1) mediates these effects. The GPER-1 specific ligand G-1 mimics the actions of E2, ICI 182,780, and TAM on ERRα expression, and changing the levels of GPER-1 mRNA by overexpression or small interfering RNA knockdown affected the expression of ERRα accordingly. Utilizing inhibitors, we delineate a different downstream pathway for ER agonist and ER antagonist-triggered signaling through GPER-1. We also find differential histone acetylation and transcription factor recruitment at distinct nucleosomes of the ERRα promoter, depending on whether the cells are activated with E2 or with ER antagonists. These findings provide insight into the molecular mechanisms of GPER-1/ERRα-mediated signaling and may be relevant to what happens in breast cancer cells escaping inhibitory control by TAM.

scholarly journals G-Protein Coupled Estrogen Receptor in Breast Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 306 ◽  
Author(s):  
Li-Han Hsu ◽  
Nei-Min Chu ◽  
Yung-Feng Lin ◽  
Shu-Huei Kao
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
G Protein ◽  
Growth Factor Receptor ◽  
Tamoxifen Resistance ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Cancer Tissues ◽  
G Protein Coupled ◽  
Positive Breast Cancer

The G-protein coupled estrogen receptor (GPER), an alternate estrogen receptor (ER) with a structure distinct from the two canonical ERs, being ERα, and ERβ, is expressed in 50% to 60% of breast cancer tissues and has been presumed to be associated with the development of tamoxifen resistance in ERα positive breast cancer. On the other hand, triple-negative breast cancer (TNBC) constitutes 15% to 20% of breast cancers and frequently displays a more aggressive behavior. GPER is prevalent and involved in TNBC and can be a therapeutic target. However, contradictory results exist regarding the function of GPER in breast cancer, proliferative or pro-apoptotic. A better understanding of the GPER, its role in breast cancer, and the interactions with the ER and epidermal growth factor receptor will be beneficial for the disease management and prevention in the future.

scholarly journals Differential expression of G protein-coupled receptor associated sorting protein 2 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
G Protein ◽  
Normal Breast ◽  
Differentially Expressed ◽  
G Protein Coupled Receptor ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
Mutational Burden ◽  
G Protein Coupled

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding G protein-coupled receptor associated sorting protein 2, GPRASP2, when comparing primary tumors of the breast to the tissue of origin, the normal breast. GPRASP2 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. GPRASP2 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of GPRASP2 in primary tumors of the breast was correlated with overall survival in black patients with high mutational burden, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by race and mutational burden. GPRASP2 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

scholarly journals Differential expression of G-protein coupled receptor 124 in cancers of the breast.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Differential Expression ◽  
G Protein ◽  
Survival Data ◽  
Normal Breast ◽  
Differentially Expressed ◽  
G Protein Coupled Receptor ◽  
Significant Differential Expression ◽  
Primary Tumors ◽  
G Protein Coupled

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding G-protein coupled receptor 124, GPR124, when comparing primary tumors of the breast to the tissue of origin, the normal breast. GPR124 mRNA was present at significantly lower quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of GPR124 in primary tumors of the breast was correlated with overall survival in patients with basal subtype cancer, demonstrating a relationship between primary tumor expression of a differentially expressed gene and patient survival outcomes influenced by molecular subtype. GPR124 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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