Correlation Between the Overexpression of Epidermal Growth Factor Receptor and Mesenchymal Makers in Endometrial Carcinoma

Overview

Journal J Gynecol Oncol

Specialties Gynecology & Obstetrics
Oncology

Date 2014 Jan 25

PMID 24459579

Citations 8

Authors

Wei-Ning Yang

Zhi-Hong Ai

Juan Wang

Yan-Li Xu

Yin-Cheng Teng

Affiliations

Soon will be listed here.

Abstract

Objective: The objective of this study was to evaluate the effect of overexpression of epidermal growth factor receptor (EGFR) on the expression of epithelial cell markers (E-cadherin and α-catenin) and mesenchymal cell markers (N-cadherin and vimentin) in endometrial carcinoma.

Methods: The expression of all 4 markers was evaluated in EGFR overexpressing Ishikawa cells, control Ishikawa cells, and KLE cells using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The expression of these 4 markers was also determined in cancerous tissues of patients with endometrial carcinoma using immunohistochemical staining.

Results: Ishikawa cells transfected with EGFR showed decreased expression of E-cadherin and α-catenin and increased expression of N-cadherin and vimentin compared with control Ishikawa cells (p<0.01 for all). The expression of N-cadherin and vimentin was higher and the expression of E-cadherin and α-catenin was lower in stage II-III than stage I and in grade II-III than grade I endometrial carcinoma tissue (p<0.01 for all).

Conclusion: Decreased expression of epithelial markers (E-cadherin and α-catenin) and increased expression of mesenchymal markers (N-cadherin and vimentin) were observed in human endometrial carcinoma tissue. These findings correlate with high EGFR expression in cultured endometrial carcinoma cells.

Citing Articles

A New Benzo[6,7]oxepino[3,2-b] Pyridine Derivative Induces Apoptosis in Canine Mammary Cancer Cell Lines.

Jianpraphat N, Supsavhad W, Ngernmeesri P, Siripattarapravat K, Soontararak S, Akrimajirachoote N Animals (Basel). 2024; 14(3).

PMID: 38338029 PMC: 10854894. DOI: 10.3390/ani14030386.

Single-cell profiling of low-stage endometrial cancers identifies low epithelial vimentin expression as a marker of recurrent disease.

Lien H, Berg H, Halle M, Trovik J, Haldorsen I, Akslen L EBioMedicine. 2023; 92:104595.

PMID: 37146405 PMC: 10277918. DOI: 10.1016/j.ebiom.2023.104595.

The role of GnRH metabolite, GnRH-(1-5), in endometrial cancer.

Cho-Clark M, Watkins A, Wu T Front Endocrinol (Lausanne). 2023; 14:1183278.

PMID: 37124730 PMC: 10140499. DOI: 10.3389/fendo.2023.1183278.

The Cross-Talk Between EGFR and E-Cadherin.

Moreno M, Bulgakova N Front Cell Dev Biol. 2022; 9:828673.

PMID: 35127732 PMC: 8811214. DOI: 10.3389/fcell.2021.828673.

Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses.

Lottini T, Iorio J, Lastraioli E, Carraresi L, Duranti C, Sala C Sci Rep. 2021; 11(1):8847.

PMID: 33893331 PMC: 8065064. DOI: 10.1038/s41598-021-87492-5.

References

Ai Z, Wang J, Wang Y, Lu L, Tong J, Teng Y . Overexpressed epidermal growth factor receptor (EGFR)-induced progestin insensitivity in human endometrial carcinoma cells by the EGFR/mitogen-activated protein kinase signaling pathway. Cancer. 2010; 116(15):3603-13. DOI: 10.1002/cncr.25220. View

Tsukamoto H, Shibata K, Kajiyama H, Terauchi M, Nawa A, Kikkawa F . Irradiation-induced epithelial-mesenchymal transition (EMT) related to invasive potential in endometrial carcinoma cells. Gynecol Oncol. 2007; 107(3):500-4. DOI: 10.1016/j.ygyno.2007.08.058. View

Saitoh M, Shirakihara T, Miyazono K . Regulation of the stability of cell surface E-cadherin by the proteasome. Biochem Biophys Res Commun. 2009; 381(4):560-5. DOI: 10.1016/j.bbrc.2009.02.098. View

Yang S, Thiel K, De Geest K, Leslie K . Endometrial cancer: reviving progesterone therapy in the molecular age. Discov Med. 2011; 12(64):205-12. View

Boyer B, Valles A, Edme N . Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol. 2000; 60(8):1091-9. DOI: 10.1016/s0006-2952(00)00427-5. View

Kang Y, Massague J . Epithelial-mesenchymal transitions: twist in development and metastasis. Cell. 2004; 118(3):277-9. DOI: 10.1016/j.cell.2004.07.011. View

Cavallaro U, Schaffhauser B, Christofori G . Cadherins and the tumour progression: is it all in a switch?. Cancer Lett. 2002; 176(2):123-8. DOI: 10.1016/s0304-3835(01)00759-5. View

Oft M, Heider K, Beug H . TGFbeta signaling is necessary for carcinoma cell invasiveness and metastasis. Curr Biol. 1998; 8(23):1243-52. DOI: 10.1016/s0960-9822(07)00533-7. View

Nicholson R, Staka C, Boyns F, Hutcheson I, Gee J . Growth factor-driven mechanisms associated with resistance to estrogen deprivation in breast cancer: new opportunities for therapy. Endocr Relat Cancer. 2004; 11(4):623-41. DOI: 10.1677/erc.1.00778. View

10.

Singh A, Settleman J . EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010; 29(34):4741-51. PMC: 3176718. DOI: 10.1038/onc.2010.215. View

11.

Garber K . Epithelial-to-mesenchymal transition is important to metastasis, but questions remain. J Natl Cancer Inst. 2008; 100(4):232-3, 239. DOI: 10.1093/jnci/djn032. View

12.

Hipp S, Walch A, Schuster T, Losko S, Laux H, Bolton T . Activation of epidermal growth factor receptor results in snail protein but not mRNA overexpression in endometrial cancer. J Cell Mol Med. 2009; 13(9B):3858-67. PMC: 4516533. DOI: 10.1111/j.1582-4934.2008.00526.x. View

13.

Dedes K, Wetterskog D, Ashworth A, Kaye S, Reis-Filho J . Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011; 8(5):261-71. DOI: 10.1038/nrclinonc.2010.216. View

14.

Scholten A, Aliredjo R, Creutzberg C, Smit V . Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable prognostic factor in endometrial carcinoma. Int J Gynecol Cancer. 2006; 16(3):1379-85. DOI: 10.1111/j.1525-1438.2006.00406.x. View

15.

Teng Y, Zeisberg M, Kalluri R . Transcriptional regulation of epithelial-mesenchymal transition. J Clin Invest. 2007; 117(2):304-6. PMC: 1783811. DOI: 10.1172/JCI31200. View

16.

Savagner P . The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol. 2010; 21 Suppl 7:vii89-92. PMC: 3379967. DOI: 10.1093/annonc/mdq292. View

17.

Jing Y, Han Z, Zhang S, Liu Y, Wei L . Epithelial-Mesenchymal Transition in tumor microenvironment. Cell Biosci. 2011; 1:29. PMC: 3179439. DOI: 10.1186/2045-3701-1-29. View

18.

Fromowitz F, Viola M, Chao S, Oravez S, Mishriki Y, Finkel G . ras p21 expression in the progression of breast cancer. Hum Pathol. 1987; 18(12):1268-75. DOI: 10.1016/s0046-8177(87)80412-4. View

19.

Bansal N, Yendluri V, Wenham R . The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2008; 16(1):8-13. DOI: 10.1177/107327480901600102. View

20.

Frixen U, Behrens J, Sachs M, Eberle G, Voss B, Warda A . E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991; 113(1):173-85. PMC: 2288921. DOI: 10.1083/jcb.113.1.173. View