Efek Pemberian Tamoxifen Citrate terhadap Ekspresi mRNA GPER-1, Snai1 dan CDH1 pada Lini Sel Kanker Payudara MCF-7 Tinjauan Terhadap Penanda Awal Epithelial-Mesenchymal Transition (EMT)

Sri Yuli Purnama, dr. Dwi Aris Agung Nugrahaningsih, M.Sc, Ph.D.; Dr.rer.nat.dr. Dyah Laksmi Dewi, M.Sc., Sp.B

2025 | Tesis | S2 Ilmu Kedokteran Dasar dan Biomedis

Latar belakang: Pada pasien kanker payudara yang menerima terapi tamoxifen, ekspresi GPER-1 dikaitkan dengan resistensi obat dan penurunan kelangsungan hidup bebas kekambuhan (relapse-free survival/RFS). Aktivasi GPER-1 oleh tamoxifen memicu jalur pensinyalan non-genomik melalui PI3K/AKT dan MAPK, yang diduga berperan dalam induksi epithelial–mesenchymal transition (EMT). EMT ditandai dengan peningkatan ekspresi SNAI1 (Snail) dan penurunan CDH1 (E-cadherin), serta berkontribusi terhadap fenotip sel yang lebih migratorik dan invasif. Deteksi resistensi umumnya terjadi pada tahap lanjut ketika perubahan molekuler bersifat irreversibel, sehingga penting untuk dilakukan identifikasi mekanisme awal seperti aktivasi EMT. Penelitian ini mengevaluasi respons seluler pada fase awal paparan tamoxifen untuk mengungkap dinamika awal proses EMT yang terlibat dalam resistensi terapi.

Tujuan: Penelitian ini bertujuan untuk mengetahui efek pemberian tamoxifen citrate terhadap ekspresi mRNA GPER-1, SNAI1, dan CDH1 sebagai penanda EMT pada sel kanker payudara MCF-7.

Metode: Sel MCF-7 ditumbuhkan dalam media (DMEM +10?S) kemudian diberi perlakuan tamoxifen dengan konsentrasi 17,26 µM selama 48 jam. Setelah perlakuan, RNA total diekstraksi, disintesis menjadi cDNA, dan selanjutnya dianalisis ekspresi gen GPER-1, SNAI1, dan CDH1 menggunakan metode qRT-PCR, dengan ?-actin sebagai gen kontrol internal. Analisis ekspresi gen dilakukan menggunakan metode 2^-??Ct, dan perbedaan antar kelompok dianalisis menggunakan uji Independent T-test dengan nilai p < 0>

Hasil: Ekspresi mRNA GPER-1 signifikan (p<0>

Kesimpulan: Ekspresi mRNA GPER-1, SNAI1 dan CDH1 signifikan lebih tinggi setelah paparan tamoxifen citrate pada lini sel kanker payudara MCF-7 yang mengarah pada dugaan bahwa EMT masih dalam tahap inisiasi. 

Background : In breast cancer patients receiving tamoxifen therapy, GPER-1 expression has been associated with drug resistance and reduced relapse-free survival (RFS). Activation of GPER-1 by tamoxifen initiates non-genomic signaling pathways, particularly through PI3K/AKT and MAPK, which are thought to contribute to the induction of epithelial–mesenchymal transition (EMT). EMT is characterized by increased expression of SNAI1 (Snail) and decreased expression of CDH1 (E-cadherin), and contributes to a more migratory and invasive cellular phenotype. Resistance is typically detected at a later stage when molecular alterations become irreversible, highlighting the importance of identifying early mechanisms such as EMT activation. This study evaluates cellular responses during the early phase of tamoxifen exposure to reveal the initial dynamics of therapy resistance. 

Objective: This study aimed to investigate the effect of 48-hour tamoxifen exposure on the mRNA expression levels of GPER-1, SNAI1, and CDH1 as markers of EMT in MCF-7 breast cancer cells.

Methods: MCF-7 cells were cultured in DMEM supplemented with 10?S, then treated with 17.26 µM tamoxifen for 48 hours. Total RNA was extracted, converted into cDNA, and the expression of GPER-1, SNAI1, and CDH1 was analyzed using quantitative real-time PCR (qRT-PCR), with ?-actin as the internal control gene. Gene expression was calculated using the 2^-??Ct method, and differences between groups were analyzed using the Independent T-test with a significance level of p < 0>

Results: The mRNA expression of GPER-1 was significantly higher (p < 0>

Conclusion: The mRNA expression levels of GPER-1, SNAI1, and CDH1 were significantly higher following 48 hours of tamoxifen citrate exposure in MCF-7 breast cancer cells suggesting that EMT may still be in its initiation stage.

Kata Kunci : Kanker payudara, GPER-1, SNAI1, CDH1, Tamoxifen, EMT