Role of EMP2 and Del-1 in Tamoxifen-resistant - Breast Cancer Cells

Sep 23, 2026

Uploaded by hdkawk

Endocrine resistance is a major clinical barrier in hormone receptor-positive breast cancer, yet the regulatory pathways interacting with developmental endothelial locus-1 (Del-1) remain unclear. This study used RNA sequencing in tamoxifen-resistant (TAMR) MCF-7 cells after Del-1 knockdown to define Del-1-associated molecular components. Among up-regulated genes, epithelial membrane protein 2 (EMP2) was examined by RT-PCR and siRNA-mediated functional assays. Results show coordinated EMP2/Del-1 regulation and increased colony formation when either is suppressed, linking the Del-1–EMP2 axis to cancer stemness and potential therapeutic targeting.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

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Abstract

Background/Aim

Materials and Methods

Results

Conclusion

Introduction

doi: 10.21873/invivo.14429 Role of EMP2 and Del-1 in Tamoxifen-resistant Breast Cancer Cells IN HEE LEE1*, JIEUN KANG2*, JEEYEON LEE3, BYEONGJU KANG3, JOON SUK MOON3, HO YONG PARK3, EUNAE KIM4, SEOL-HWA JEONG4, YEE SOO CHAE1 and SOO JUNG LEE1 1 Department of Oncology/Hematology, Kyungpook National Chilgok University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 2 Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; 3 Breast & Thyroid Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; 4Cell & Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea Abstract Background/Aim: Endocrine resistance remains a major clinical challenge in hormone receptor-positive (HR+) breast cancer. Although developmental endothelial locus-1 (Del-1) has been implicated in endocrine resistance, the regulatory pathways interacting with Del-1 remain poorly defined. This study aimed to identify molecular components associated with Del-1-driven resistance by performing RNA sequencing in tamoxifen-resistant (TAMR) breast cancer cells following Del-1 knockdown. Materials and Methods: RNA sequencing was conducted in TAMR MCF-7 cells following Del-1 silencing to identify Del- 1-regulated pathways in endocrine-resistant disease. Among the genes up-regulated after Del-1 suppression, epithelial membrane protein 2 (EMP2) was selected for further investigation due to its reported roles in cellular adhesion, metabolic signaling, and cancer stemness. Gene expression changes were validated using reverse transcription polymerase chain reaction (RT-PCR) . Functional studies were performed using small interfering RNA (siRNA) -mediated knockdown of EMP2 or Del-1, followed by proliferation and clonogenic assays. Results: Both EMP2 and Del-1 were up-regulated in luminal breast cancer cell lines. Suppression of Del-1 increased EMP2 expression inTAMR cells, consistent with RNA-seq findings. Notably, EMP2 suppression resulted in an increase in Del-1 expression, suggesting a potential regulatory feedback loop. Furthermore, knockdown of either Del-1 or EMP2 substantially enhanced colony formation in TAMR cells compared with controls. Conclusion: EMP2 may be involved in the regulation of Del-1 expression in TAMR breast cancer cells. Modulation of Del-1 or EMP2 influences cancer stemness inTAMR cells, underscoring the Del-1-EMP2 axis as a potential therapeutic target to overcome endocrine resistance. Keywords: Del-1, EMP2, breast cancer, endocrine resistance, stemness. *These Authors contributed equally to this study. Soo Jung Lee, MD, PhD, Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukno, Buk-gu, Daegu 41404, Republic of Korea. Tel: +82 532002168, axec:i82ve5d32M0a0y280, 2290,e26-m| aiRle:mviasjestio0ed Jun3e@2,gmai202[l](l6.co|)[6](l6.co|)[.co](l6.co|)[|](l6.co|)mAccepted June 17, 2026 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ©2026 The Author(s) . Published by the International Institute of Anticancer Research. Introduction Breast cancer is a heterogeneous disease, and hormone receptor-positive (HR+) tumors represent the most common subtype (1) . Tamoxifen, a selective estrogen receptor modulator, is the most frequently prescribed endocrine therapy for premenopausal women with HR+ breast cancer. Despite its proven clinical benefit, a substantial proportion of patients eventually develop tamoxifen resistance, resulting in therapeutic failure and cancer recurrence (2, 3) . Understanding the molecular mechanisms underlying this resistance is essential for identifying novel targetsand improving patient outcomes. Previous st

FAQs

What was the study’s primary goal regarding Del-1 in tamoxifen-resistant breast cancer cells?

To identify molecular components associated with Del-1-driven endocrine resistance by analyzing TAMR breast cancer cells after Del-1 knockdown with RNA sequencing.

How were EMP2 and Del-1 functionally tested in tamoxifen-resistant cells?

The study validated gene expression changes with RT-PCR and performed siRNA-mediated knockdown of Del-1 or EMP2, followed by proliferation and clonogenic (colony formation) assays.

What key regulatory relationship did the study observe between Del-1 and EMP2?

Del-1 suppression increased EMP2 expression, and EMP2 suppression increased Del-1 expression, suggesting a potential regulatory feedback loop.

Sep 23, 2026

Uploaded by hdkawk