Research Article


DOI :10.26650/experimed.2021.864886   IUP :10.26650/experimed.2021.864886    Full Text (PDF)

Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression

Nadir GülFranz Theuring

Objective: As a distinct cellular signaling model, a receptor crosstalk between G protein-coupled receptors (GPCR) and epidermal growth factor receptor (EGFR) has been demonstrated in various in vitro studies. In addition, recent in vitro studies had focused on the signaling pathways of endothelin-1 (ET-1) in the pathophysiology of cancer. Accordingly, a growing interest in the analysis of the receptor crosstalk between ET-1 receptors and EGFR and functional consequences of EGFR activation of proliferative diseases evoked us to the analysis of this phenomenon in vivo. Materials and Methods: We performed a comparative study between ET-1 transgenic mice and control mice during the late pregnancy (n=7), early lactation (n=6) the mid of lactation (n=10) and involution day 14 (n=7) periods. Hematoxylin and eosin (HE)- stained parallel sections from mammary glands were microscopically examined. The key signal proteins (ETAR, ETBR, ERK1/2, pEGFR) in transactivation of EGFR were analyzed employing Western blot techniques. Genes (amphiregulin, TGFa, EGF, HB-EGF, ADAM 17) known to play an important role in these activities were analyzed using real-time PCR (RT-PCR) techniques. Results: ET-1 transgenic mice exhibited hyperproliferative lesions (lactational hyperplasia) during the middle of the lactation period. Our RT-PCR analyses showed a prominent up regulation of amphiregulin and ADAM 17 in ET-1 transgenic mice. Moreover, we found higher EGFR and ERKs activations in the transgenic mammary glands. Conclusion: This study highlights a causative effect of upregulated ET-1 gene expression on the induction of proliferative lesions via EGFR transactivation in mammary glands. Further, ET-1 overexpression induced an upregulation of amphiregulin and ADAM17 expressions in the transgenic mammary glands. These results suggests that the enhanced ET-1 gene expression and its receptors might have a crucial role in proliferative diseases maintaining EGFR activation.

DOI :10.26650/experimed.2021.864886   IUP :10.26650/experimed.2021.864886    Full Text (PDF)

ET-1 Aşırı Anlatımının Bir Sonucu Olan, Sinyal Çapraz Etkileşimi ‘Crosstalk’, Fare Meme Bezlerinde Proliferatif Lezyonların Oluşumunu Teşvik Eder

Nadir GülFranz Theuring

Amaç: Farklı bir hücresel sinyalleşme modeli olarak, G proteini ile eşleşmiş reseptörler (GPCR) ve epidermal growth faktör reseptör (EGFR) arasındaki reseptör çapraz etkileşimi (crosstalk), çeşitli in vitro çalışmalarda gösterilmiştir. Ayrıca, son dönem in vitro çalışmalar, endotelin-1 (ET-1) sinyal yolağının kanser patofizyolojisi üzerindeki ilişkisine odaklanmıştır. Bu bağlamda, ET-1 reseptörleri ve EGFR arasındaki reseptör çapraz etkileşim analizine ve EGFR aktivasyonunun fonksiyonel sonuçlarından proliferatif hastalıklara olan artan ilgi, bize bu fenomeni in vivo analiz etme fikrini oluşturmuştur. Gereç ve Yöntem: ET-1 transgenik fareler ve kontrol fareleri arasında geç gebelik dönemi (n=7 ), erken laktasyon dönemi (n=6 ) orta dönem laktasyon (n=10) ve involusyon 14. gün (n=7) sırasında karşılaştırmalı bir çalışma gerçekleştirildi. Meme bezlerinden hematoksilen-eozin (HE) ile boyanmış paralel kesitler mikroskobik olarak incelendi. EGFR'nin transaktivasyonunda görev alan anahtar sinyal proteinleri (ETAR, ETBR, ERK1/2, pEGFR), Western blot teknikleri kullanılarak analiz edildi. Bu aktivitelerde önemli bir rol oynadığı bilinen genler (amfiregulin, TGFa, EGF, HB-EGF, ADAM 17), gercek zamanlı polimeraz zincir reaksiyonu (RT-PCR) teknikleri kullanılarak analiz edildi. Bulgular: ET-1 transgenik fareler, laktasyon döneminin ortasında hiper-proliferatif lezyonlar (laktasyonel hiperplazi) geliştirdi. RT-PCR analizlerimiz, transgenik farelerde amfiregulin ve ADAM 17 gen anlatımlarında belirgin bir artış olduğunu göstermektedir. Ayrıca transgenik meme bezlerinde daha yüksek EGFR ve ERKs aktivasyonları tespit edilmiştir. Sonuç: Bu çalışma, yüksek seviyede ET-1 gen anlatımının EGFR yi transaktive etme yoluyla meme bezlerinde proliferatif lezyonları tetiklediğini göstermektedir. Ayrıca, ET-1 aşırı anlatımı, transgen meme bezlerinde amfiregulin ve ADAM17 anlatımlarının belirgin bir şekilde yukarı regülasyonuna neden olmaktadır. Bu sonuçlar bize ET-1 gen ekspresyonunu ve reseptörlerinin EGFR aktivasyonunu sağlayarak proliferatif hastalıklarda önemli bir role sahip olduğunu göstermektedir.


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APA

Gül, N., & Theuring, F. (2021). Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression. Experimed, 11(1), 1-11. https://doi.org/10.26650/experimed.2021.864886


AMA

Gül N, Theuring F. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression. Experimed. 2021;11(1):1-11. https://doi.org/10.26650/experimed.2021.864886


ABNT

Gül, N.; Theuring, F. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression. Experimed, [Publisher Location], v. 11, n. 1, p. 1-11, 2021.


Chicago: Author-Date Style

Gül, Nadir, and Franz Theuring. 2021. “Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression.” Experimed 11, no. 1: 1-11. https://doi.org/10.26650/experimed.2021.864886


Chicago: Humanities Style

Gül, Nadir, and Franz Theuring. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression.” Experimed 11, no. 1 (Jul. 2021): 1-11. https://doi.org/10.26650/experimed.2021.864886


Harvard: Australian Style

Gül, N & Theuring, F 2021, 'Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression', Experimed, vol. 11, no. 1, pp. 1-11, viewed 25 Jul. 2021, https://doi.org/10.26650/experimed.2021.864886


Harvard: Author-Date Style

Gül, N. and Theuring, F. (2021) ‘Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression’, Experimed, 11(1), pp. 1-11. https://doi.org/10.26650/experimed.2021.864886 (25 Jul. 2021).


MLA

Gül, Nadir, and Franz Theuring. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression.” Experimed, vol. 11, no. 1, 2021, pp. 1-11. [Database Container], https://doi.org/10.26650/experimed.2021.864886


Vancouver

Gül N, Theuring F. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression. Experimed [Internet]. 25 Jul. 2021 [cited 25 Jul. 2021];11(1):1-11. Available from: https://doi.org/10.26650/experimed.2021.864886 doi: 10.26650/experimed.2021.864886


ISNAD

Gül, Nadir - Theuring, Franz. Signal Crosstalk Promoted Proliferative Lesions in Mouse Mammary Glands As a Consequence of ET-1 Overexpression”. Experimed 11/1 (Jul. 2021): 1-11. https://doi.org/10.26650/experimed.2021.864886



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Submitted20.01.2021
Accepted11.03.2021
Published Online27.04.2021

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