Stimulation of peroxisome proliferator-activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells Retraction in /10.3892/or.2024.8836

Zhang,Guiyu; Hou,Xinxin; Gao,Shuhong

doi:10.3892/or.2015.3729

Stimulation of peroxisome proliferator-activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells

Retraction in: /10.3892/or.2024.8836

Authors:
- Guiyu Zhang
- Xinxin Hou
- Shuhong Gao
View Affiliations

Affiliations: Department of Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai 200011, P.R. China, Department of Gynecology and Obstetrics, Dongying Honggang Hospital, Dongying, Shandong 257000, P.R. China
Published online on: January 15, 2015 https://doi.org/10.3892/or.2015.3729
Pages: 1227-1234

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) and estrogen receptor (ER) belong to a family of nuclear hormone receptors that have been demonstrated to affect each other's transcriptional activity. At present, little is known regarding the effect of PPARγ on ER-mediated transcriptional activity in endometrial carcinoma. In the present study, we aimed to demonstrate the correlation between PPARγ and ER in endometrial carcinoma and to elucidate the biological effects of abnormal expression of PPARγ on endometrial carcinoma cell lines. Immunohistochemical and western blotting methods were used to detect the expression of PPARγ, ERα and ERβ in normal and malignant endometrium. Next, we performed transient transfection to assess the interaction between PPARγ and ER in vitro. Furthermore, we examined cell migration, invasion and proliferation as a biological counterpart. PPARγ and ERα expression levels were significantly associated with pathological grade and clinical stage in endometrial carcinoma (P<0.05). Pearson correlation analysis revealed that PPARγ expression was positively correlated with ERα expression (P<0.05). Using KLE and ERα-positive cells (ECC-1), we demonstrated that the PPARγ regulation of ER expression occurred predominantly through ERα. Moreover, our findings suggest that PPARγ activation inhibited the migration, invasion and proliferation of endometrial carcinoma cells; ECC-1 cells were more sensitive to this inhibition. The present study demonstrated that PPARγ activation inhibited ERα expression in ERα-positive endometrial carcinoma cell lines. This crosstalk may facilitate the development of novel therapeutic methods targeting PPARγ in endometrial carcinoma treatment, particularly ERα-positive carcinomas.

View Figures

View References

1	Boll D, Karim-Kos HE, Verhoeven RH, et al: Increased incidence and improved survival in endometrioid endometrial cancer diagnosed since 1989 in The Netherlands: a population based study. Eur J Obstet Gynecol Reprod Biol. 166:209–214. 2013. View Article : Google Scholar
2	Gadducci A, Cosio S and Genazzani AR: Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: hormonal therapy, chemotherapy and molecularly targeted therapies. Crit Rev Oncol Hematol. 58:242–256. 2006. View Article : Google Scholar : PubMed/NCBI
3	Tavares V, Hirata MH and Hirata RD: Peroxisome proliferator-activated receptor γ (PPAR γ): molecular study in glucose homeostasis, lipid metabolism and therapeutic approach. Arq Bras Endocrinol Metabol. 51:526–533. 2007. View Article : Google Scholar : PubMed/NCBI
4	Berstein LM, Kvatchevskaya JO, Poroshina TE, Kovalenko IG, et al: Insulin resistance, its consequences for the clinical course of the disease, and possibilities of correction in endometrial cancer. J Cancer Res Clin Oncol. 130:687–693. 2004. View Article : Google Scholar : PubMed/NCBI
5	Tsukahara T and Haniu H: Peroxisome proliferator-activated receptor gamma overexpression suppresses proliferation of human colon cancer cells. Biochem Biophys Res Commun. 424:524–529. 2012. View Article : Google Scholar : PubMed/NCBI
6	Reka AK, Goswami MT, Krishnapuram R, Standiford TJ and Keshamouni VG: Molecular cross-regulation between PPAR-γ and other signaling pathways: implications for lung cancer therapy. Lung Cancer. 72:154–159. 2011. View Article : Google Scholar : PubMed/NCBI
7	Jiang Y, Huang Y, Cheng C, et al: Combination of thiazolidinedione and hydralazine suppresses proliferation and induces apoptosis by PPARγ up-expression in MDA-MB-231 cells. Exp Mol Pathol. 91:768–774. 2011. View Article : Google Scholar : PubMed/NCBI
8	Ito K, Utsunomiya H, Niikura H, Yaegashi N and Sasano H: Inhibition of estrogen actions in human gynecological malignancies: new aspects of endocrine therapy for endometrial cancer and ovarian cancer. Mol Cell Endocrinol. 340:161–167. 2011. View Article : Google Scholar
9	Shabani N, Kuhn C, Kunze S, et al: Prognostic significance of oestrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor A (PR-A) and B (PR-B) in endometrial carcinomas. Eur J Cancer. 43:2434–2444. 2007. View Article : Google Scholar : PubMed/NCBI
10	Ito K, Utsunomiya H, Yaegashi N and Sasano H: Biological roles of estrogen and progesterone in human endometrial carcinoma - new developments in potential endocrine therapy for endometrial cancer. Endocr J. 54:667–679. 2007. View Article : Google Scholar : PubMed/NCBI
11	Pearce ST and Jordan VC: The biological role of estrogen receptors α and β in cancer. Crit Rev Oncol Hematol. 50:3–22. 2004. View Article : Google Scholar : PubMed/NCBI
12	Kurebayashi J, Otsuki T, Kunisue H, Tanaka K, Yamamoto S and Sonoo H: Expression levels of estrogen receptor-α, estrogen receptor-β, coactivators, and corepressors in breast cancer. Clin Cancer Res. 6:512–518. 2000.PubMed/NCBI
13	Mann S, Laucirica R, Carlson N, et al: Estrogen receptor beta expression in invasive breast cancer. Hum Pathol. 32:113–118. 2001. View Article : Google Scholar : PubMed/NCBI
14	Lin CY, Ström A, Li Kong S, et al: Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer. Breast Cancer Res. 9:R252007. View Article : Google Scholar : PubMed/NCBI
15	Jensen EV and Jordan VC: The estrogen receptor: a model for molecular medicine. Clin Cancer Res. 9:1980–1989. 2003.PubMed/NCBI
16	Yuan H, Kopelovich L, Yin Y, Lu J and Glazer RI: Drug-targeted inhibition of peroxisome proliferator-activated receptor-gamma enhances the chemopreventive effect of anti-estrogen therapy. Oncotarget. 3:345–356. 2012.PubMed/NCBI
17	Tateishi Y, Kawabe Y, Chiba T, et al: Ligand-dependent switching of ubiquitin-proteasome pathways for estrogen receptor. EMBO J. 23:4813–4823. 2004. View Article : Google Scholar : PubMed/NCBI
18	Kato S: Estrogen receptor-mediated cross-talk with growth factor signaling pathways. Breast Cancer. 8:3–9. 2001. View Article : Google Scholar : PubMed/NCBI
19	Zhang Z, Zhou D, Lai Y, et al: Estrogen induces endometrial cancer cell proliferation and invasion by regulating the fat mass and obesity-associated gene via PI3K/AKT and MAPK signaling pathways. Cancer Lett. 319:89–97. 2012. View Article : Google Scholar : PubMed/NCBI
20	Glass CK, Holloway JM, Devary OV and Rosenfeld MG: The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell. 54:313–323. 1988. View Article : Google Scholar : PubMed/NCBI
21	Wang X and Kilgore MW: Signal cross-talk between estrogen receptor alpha and beta and the peroxisome proliferator-activated receptor gamma1 in MDA-MB-231 and MCF-7 breast cancer cells. Mol Cell Endocrinol. 194:123–133. 2002. View Article : Google Scholar : PubMed/NCBI
22	Nickkho-Amiry M, McVey R and Holland C: Peroxisome proliferator-activated receptors modulate proliferation and angiogenesis in human endometrial carcinoma. Mol Cancer Res. 10:441–453. 2012. View Article : Google Scholar
23	Mansure JJ, Nassim R and Kassouf W: Peroxisome proliferator-activated receptor γ in bladder cancer: a promising therapeutic target. Cancer Biol Ther. 8:6–15. 2009. View Article : Google Scholar : PubMed/NCBI
24	Ota K, Ito K, Suzuki T, et al: Peroxisome proliferator-activated receptor γ and growth inhibition by its ligands in uterine endometrial carcinoma. Clin Cancer Res. 12:4200–4208. 2006. View Article : Google Scholar : PubMed/NCBI
25	Brody F, Hill S, Celenski S, et al: Expression of ectonucleotide pyrophosphate phosphodiesterase and peroxisome proliferator activated receptor γ in morbidly obese patients. Surg Endosc. 21:941–944. 2007. View Article : Google Scholar : PubMed/NCBI
26	Houston KD, Copland JA, Broaddus RR, Gottardis MM, Fischer SM and Walker CL: Inhibition of proliferation and estrogen receptor signaling by peroxisome proliferator-activated receptor γ ligands in uterine leiomyoma. Cancer Res. 63:1221–1227. 2003.PubMed/NCBI
27	Keller H, Givel F, Perroud M and Wahli W: Signaling cross-talk between peroxisome proliferator-activated receptor/retinoid X receptor and estrogen receptor through estrogen response elements. Mol Endocrinol. 9:794–804. 1995.PubMed/NCBI
28	Kliewer SA, Umesono K, Noonan DJ, Heyman RA and Evans RM: Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature. 358:771–774. 1992. View Article : Google Scholar : PubMed/NCBI
29	Knapp P, Chabowski A, Blachnio-Zabielska A, Jarzabek K and Wołczyński S: Altered peroxisome-proliferator activated receptors expression in human endometrial cancer. PPAR Res. 2012:4715242012. View Article : Google Scholar : PubMed/NCBI
30	Issemann I and Green S: Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 347:645–650. 1990. View Article : Google Scholar : PubMed/NCBI
31	Saegusa M and Okayasu I: Changes in expression of estrogen receptors alpha and beta in relation to progesterone receptor and pS2 status in normal and malignant endometrium. Jpn J Cancer Res. 91:510–518. 2000. View Article : Google Scholar : PubMed/NCBI
32	Chakravarty D, Srinivasan R, Ghosh S, Rajwanshi A and Gopalan S: Estrogen receptor beta (ERbeta) in endometrial simple hyperplasia and endometrioid carcinoma. Appl Immunohistochem Mol Morphol. 16:535–542. 2008. View Article : Google Scholar : PubMed/NCBI
33	Jiang Y, Zou L, Zhang C, et al: PPARγ and Wnt/β-catenin pathway in human breast cancer: expression pattern, molecular interaction and clinical/prognostic correlations. J Cancer Res Clin Oncol. 135:1551–1559. 2009. View Article : Google Scholar : PubMed/NCBI