nach oben

Journal of Cancer Research and Clinical Oncology

Erschienen in:

01.05.2012 | Original Article

Estrogenic transmembrane receptor of GPR30 mediates invasion and carcinogenesis by endometrial cancer cell line RL95-2

verfasst von: Yin-Yan He, Gui-Qiang Du, Bin Cai, Qin Yan, Long Zhou, Xiao-Yue Chen, Wen Lu, Yi-Xia Yang, Xiao-Ping Wan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The mechanisms underlying the effects of estrogen on endometrial cancer remain undefined. Although the classical mechanism of the action of estrogen involves binding to the estrogen receptors α and β, and transduction of the signal into the cell, G protein-coupled receptor (GPR) 30 has been shown to mediate nongenomic estrogen signaling. The goal of this study was to determine the role of GPR30 signal in the basic process such as invasion and carcinogenesis of endometrial cancer.

Methods

We downregulated the expression of GPR30 in endometrial cancer cell line RL95-2 by transfection with shGPR30-pGFP-V-RS, a GPR30 antisense expression vector. The cells were then subjected to an MTT assay and a Transwell^® migration assay. And an animal model was also used to investigate the influence of downregulation of GPR30 on oncogenesis.

Results

Downregulation of GPR30 led to reduced growth and invasion by cells treated with 17β-estradiol. And the capacity of transfected RL95-2 cells to promote tumorigenesis was weakened in vivo.

Conclusions

Our data suggest that, for the endometrial cancer cell line RL95-2, GPR30 plays important roles in mediating the proliferative and invasive effects of estrogen and in tumorigenesis.

Albanito L, Madeo A, Lappano R, Vivacqua A, Rago V, Carpino A, Oprea TI, Prossnitz ER, Musti AM, Andò S, Maggiolini M (2007) G protein–coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17β-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells. Cancer Res 67:1859–1866

Baquedano MS, Saraco N, Berensztein E, Pepe C, Bianchini M, Levy E, Goñi J, Rivarola MA, Belgorosky A (2007) Identification and developmental changes of aromatase and estrogen receptor expression in prepubertal and pubertal human adrenal tissues. J Clin Endocrinol Metab 92:2215–2222PubMedCrossRef

Filardo EJ, Quinn JA, Bland KI, Frackelton AR Jr (2000) Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol 14:1649–1660PubMedCrossRef

Filardo EJ, Quinn JA, Frackelton AR Jr, Bland KI (2002) Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol 16:70–84PubMedCrossRef

Filardo EJ, Graeber CT, Quinn JA, Resnick MB, Giri D, DeLellis RA, Steinhoff MM, Sabo E (2006) Distribution of GPR30, a Seven Membrane¨CSpanning estrogen receptor, in primary breast cancer and its association with clinicopathologic determinants of tumor progression. Clin Cancer Res 12:6359–6366PubMedCrossRef

Harrington WR, Kim SH, Funk CC, Madak-Erdogan Z, Schiff R, Katzenellenbogen JA, Katzenellenbogen BS (2006) Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action. Mol Endocrinol 20:491–502PubMedCrossRef

He Y–Y, Cai B, Yang Y-X, Liu XL, Wan XP (2009) Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway. Cancer Sci 100:1051–1061PubMedCrossRef

Ignatov T, Eggemann H, Semczuk A, Smith B, Bischoff J, Roessner A, Costa SD, Kalinski T, Ignatov A (2010) Role of GPR30 in endometrial pathology after tamoxifen for breast cancer. Am J Obstet Gynecol 203:595.e9–595.e16

Kumar V, Chambon P (1988) The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell 55:145–156PubMedCrossRef

Levin ER (2005) Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol 19:1951–1959PubMedCrossRef

Lin BC, Suzawa M, Blind RD, Tobias SC, Bulun SE, Scanlan TS, Ingraham HA (2009) Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation. Cancer Res 69:5415–5423PubMedCrossRef

Pedram A, Razandi M, Levin ER (2006) Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol 20:1996–2009PubMedCrossRef

Pietras RJ, Levin ER, Szego CM (2005) Estrogen receptors and cell signaling. Science 310:51–53PubMedCrossRef

Revankar CM, Cimino DF, Sklar LA et al (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 307:1625–1630PubMedCrossRef

Sato Y, Fujiwara H, Yoshioka S, Tatsumi K, Maeda M, Fujii S (2002) Involvement of dipeptidyl peptidase IV in extravillous trophoblast invasion and differentiation. J Clin Endocrinol Metab 87:4287–4296PubMedCrossRef

Shang Y (2006) Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat Rev Cancer 6:360–368PubMedCrossRef

Shang Y (2007) Hormones and cancer. Cell Res 17:277–279PubMedCrossRef

Smith HO, Leslie KK, Singh M, Qualls CR, Revankar CM, Joste NE, Prossnitz ER (2007) GPR30: a novel indicator of poor survival for endometrial carcinoma. Am J Obstet Gynecol 196:386. e1–386.e11

Thomas P, Pang Y, Filardo E, Dong J (2005) Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology 146:624–632PubMedCrossRef

Vivacqua A, Bonofiglio D, Recchia AG, Musti AM, Picard D, Andò S, Maggiolini M (2005) The G protein-coupled receptor GPR30 mediates the proliferative effects induced by 17-estradiol and hydroxytamoxifen in endometrial cancer cells. Mol Endocrinol 20:631–646PubMedCrossRef

Vivacqua A, Bonofiglio D, Albanito L, Madeo A, Rago V, Carpino A, Musti AM, Picard D, Andò S, Maggiolini M (2006) 17β-Estradiol, genistein, and 4-hydroxytamoxifen induce the proliferation of thyroid cancer cells through the g protein-coupled receptor GPR30. Mol Pharmacol 70:1414–1423PubMedCrossRef

Vivacqua A, Lappano R, De Marco P, Sisci D, Aquila S, De Amicis F, Fuqua SA, Andò S, Maggiolini M (2009) G protein-coupled receptor 30 expression is up-regulated by EGF and TGF alpha in estrogen receptor {alpha}-positive cancer cells. Mol Endocrinol 23:1815–1826PubMedCrossRef

Wang C, Prossnitz ER, Roy SK (2007) Expression of G protein-coupled receptor 30 in the hamster ovary: differential regulation by gonadotropins and steroid hormones. Endocrinology 148:4853–4864PubMedCrossRef

Titel: Estrogenic transmembrane receptor of GPR30 mediates invasion and carcinogenesis by endometrial cancer cell line RL95-2
verfasst von: Yin-Yan He
Gui-Qiang Du
Bin Cai
Qin Yan
Long Zhou
Xiao-Yue Chen
Wen Lu
Yi-Xia Yang
Xiao-Ping Wan
Publikationsdatum: 01.05.2012
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 5/2012
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1133-7

Neu im Fachgebiet Onkologie

23.04.2024 | Medikamente in Schwangerschaft und Stillzeit | Nachrichten

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Estrogenic transmembrane receptor of GPR30 mediates invasion and carcinogenesis by endometrial cancer cell line RL95-2

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2012

Effectiveness and safety of pemetrexed-based doublet versus pemetrexed alone as second-line treatment for advanced non-small-cell lung cancer: a systematic review and meta-analysis

A novel xenograft model with intrinsic vascularisation for growing undifferentiated pleomorphic sarcoma NOS in mice

MicroRNA-223 functions as an oncogene in human gastric cancer by targeting FBXW7/hCdc4

Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines

Tumor suppressor gene BLU is frequently downregulated by promoter hypermethylation in myelodysplastic syndrome

Pseudolaric acid B inhibits inducible cyclooxygenase-2 expression via downregulation of the NF-κB pathway in HT-29 cells

Neu im Fachgebiet Onkologie

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Stufenschema weist Prostatakarzinom zuverlässig nach

Update Onkologie