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

Year 2021, Volume: 11 Issue: 1, 1 - 11, 03.05.2021
https://doi.org/10.26650/experimed.2021.864886

Abstract

Objective: As a distinct cellular signaling model, a receptor cross-talk 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 re-ceptor 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 microscop-ically examined. The key signal proteins (ETAR, ETBR, ERK1/2, pEG-FR) 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 amphi-regulin and ADAM17 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 overexpres-sion induced an upregulation of amphiregulin and ADAM17 expres-sions 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.

Supporting Institution

Charite Universitätsmedizin Berlin

References

  • 1. Itoh Y, Kimura C, Onda H, Fujino M. Canine endothelin-2: cDNA sequence for the mature peptide. Nucleic Acids Res 1989; 17(13): 5389. [CrossRef] google scholar
  • 2. Takaoka M, Miyata Y, Takenobu Y, Ikegawa R, Matsumura Y, Mori-moto S. Mode of cleavage of pig big endothelin-1 by chymotry-psin. Production and degradation of mature endothelin-1. Bioc-hem J 1990; 270(2): 541-4. [CrossRef] google scholar
  • 3. Battistini B, D’Orleans-Juste P, Sirois P. Endothelins: circulating plasma levels and presence in other biologic fluids. Lab Invest 1993; 68(6): 600-28. google scholar
  • 4. Moraitis S, Miller WR, Smyth JF, Langdon SP. Paracrine regulation of ovarian cancer by endothelin Eur J Cancer 1999; 35(9): 1381-7. [CrossRef] google scholar
  • 5. Marsault R, Feolde E, Frelin C. Receptor externalization determines sustained contractile responses to endothelin-1 in the rat aorta. Am J Physiol 1993; 264(3 Pt 1): C687-93. [CrossRef] google scholar
  • 6. Yanagisawa M & Masaki T. Endothelin, a novel endothelium-deri-ved peptide. Pharmacological activities, regulation and possible roles in cardiovascular control. Biochem Pharmacol 1989; 38(12): 1877-83. [CrossRef] google scholar
  • 7. Rozengurt E. Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol 2007; 213(3): 589-602. [CrossRef] google scholar
  • 8. Cazaubon SM, Ramos-Morales F, Fischer S, Schweighoffer F, Stros-berg AD, Couraud PO. Endothelin induces tyrosine phosphoryla-tion and Grb2 association of Shc in astrocytes. J Biol Chem 1994; 269: 24805-9. [CrossRef] google scholar
  • 9. Daaka Y. G proteins in cancer: the prostate cancer paradigm. Sci STKE 2004; re2. [CrossRef] google scholar
  • 10. Wiesen JF, Young P, Werb Z, Cunha GR. Signaling through the stro-mal epidermal growth factor receptor is necessary for mammary ductal development. Development 1999; 126: 335-44. google scholar
  • 11. Hynes NE & Watson CJ. Mammary gland growth factors: roles in normal development and in cancer. Cold Spring Harb Perspect Biol 2010; 2(8): a003186. [CrossRef] google scholar
  • 12. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature. 1996; 379(6565): 557-60. [CrossRef] google scholar
  • 13. Zhang Q, Thomas SM, Lui VW, Xi S, Siegfried JM, Fan H, et al. Phosphorylation of TNF-alpha converting enzyme by gastrin-re-leasing peptide induces amphiregulin release and EGF receptor activation Proc Natl Acad Sci U S A. 2006; 103(18): 6901-6. google scholar
  • 14. Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci U S A. 2007; 104(13): 5455-60. [CrossRef] google scholar
  • 15. Greco S, Muscella A, Elia MG, Salvatore P, Storelli C, Mazzotta A. Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells. J Cell Physiol 2003; 196: 370-7. [CrossRef] google scholar
  • 16. Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S. PKC-z is required for angiotensin II-induced activation of ERK and synthesis of C-FOS in MCF-7 cells. J Cell Physiol 2003; 197: 61-8. [CrossRef] google scholar
  • 17. Rosano L, Di Castro V, Spinella F, Tortora G, Nicotra MR, Natali PG, et al. Combined targeting of endothelin A receptor and epidermal growth factor receptor in ovarian cancer shows enhanced antitu-mor activity. Cancer Res 2007; 67(13): 6351-9. [CrossRef] google scholar
  • 18. Peles E & Yarden Y. Neu and its ligands: from an oncogene to neu-ral factors. Bioessays 1993; 15: 815-24. [CrossRef] google scholar
  • 19. Cohen S. Nobel lecture. Epidermal growth factor Biosci Rep 1986; 6(12): 1017-28. [CrossRef] google scholar
  • 20. Luetteke NC, Qiu TH, Fenton SE, Troyer KL, Riedel RF, Chang A, et al. Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. Development 1999; 126: 2739-50. google scholar
  • 21. Higashiyama S, Lau K, Besner GE Abraham JA, Klagsbrun M. Stru-cture of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem 1992; 267(9): 6205-12. [CrossRef] google scholar
  • 22. Shoyab M, McDonald VL, Bradley JG, Todaro GJ. Amphiregulin: a bifunctional growth- modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adeno-carcinoma cell line MCF-7. Proc Natl Acad Sci U.S.A. 1988; 85(17): 6528-32. [CrossRef] google scholar
  • 23. Riese DJ, Komurasaki T, Plowman GD, Stern D. Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epi-regulin is regulated by ErbB2. J Biol Chem 1998; 273(18): 1128894. [CrossRef] google scholar
  • 24. Strachan L, Murison JG, Prestidge RL, Sleeman MA, Watson JD, Kumble KD. Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem 2001; 276(21): 18265-71. [CrossRef] google scholar
  • 25. Salomon DS, Bianco C, De Santis M. Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland develop-ment and neoplasia. Bioessays 1999; 21(1): 61-70. [CrossRef] google scholar
  • 26. Troyer KL & Lee DC. Regulation of mouse mammary gland de-velopment and tumorigenesis by the ERBB signaling network. J Mammary Gland Biol Neoplasia 2001; 6(1): 7-21. google scholar
  • 27. Hocher B, Thöne-Reineke C, Rohmeiss P, Schmager F, Slowinski T, Burst V, et al. Endothelin-1 transgenic mice develop glomerulosc-lerosis, interstitial fibrosis, and renal cysts but not hypertension. J Clin Invest 1997; 99(6): 1380-9. [CrossRef] google scholar
  • 28. Pfaffl MW, Horghan GW, Dempfle L. Relative expression software tool (REST) for group- wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Resear-ch 2002; 30(9): e36. [CrossRef] google scholar
  • 29. Fowler, KJ, Walker F, Alexander W, Hibbs ML, Nice EC, Bohmer RM, et al. A mutation in the epidermal growth factor receptor in wa-ved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation. Proc Natl Acad Sci USA 1995; 92: 1465-9. [CrossRef] google scholar
  • 30. Xie W, Paterson AJ, Chin E, Nabell LM, Kudlow JE. Targeted exp-ression of a dominant negative epidermal growth factor recep-tor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol 1997; 11: 1766-81. [CrossRef] google scholar
  • 31. Tsujioka H, Yotsumoto F, Shirota K, Horiuchi S, Yoshizato T, Kuroki M, et al. Emerging strategies for ErbB ligand-based targeted the-rapy for cancer. Anticancer Res 2010; 30(8): 3107-12. google scholar
  • 32. D’Cruz CM, Moody SE, Master SR, Hartman JL, Keiper EA, Imielins-ki MB, et al. Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland. Mol Endocrinol 2002; 16(9): 2034-51. [CrossRef] google scholar
  • 33. Schroeder JA & Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ 1998; 9: 451-64. google scholar
  • 34. Bagnato A, Tecce R, Di Castro V, Catt KJ. Activation of mitogenic signaling by endothelin 1 in ovarian carcinoma cells. Cancer Res 1997; 57(7): 1306-11. google scholar
  • 35. Alanen K, Deng DX, Chakrabarti S. Augmented expression of en-dothelin-1, endothelin-3 And the endothelin-B receptor in breast carcinoma. Histopathology 2000; 36(2): 161-7. [CrossRef] google scholar
  • 36. Bagnato A, Rosano L, Di Castro V, Albini A, Salani D, Varmi M, et al. Endothelin receptor blockade inhibits proliferation of Kaposi’s sarcoma cells. Am J Pathol 2001; 158(3): 841-7. [CrossRef] google scholar
  • 37. Nelson J, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer 2003; 3(2): 110-6. [CrossRef] google scholar
  • 38. Hagemann T, Binder C, Binder L, Pukrop T, Trumper L, Grimshaw, MJ. Expression of endothelins and their receptors promotes an invasive Phenotype of breast tumor cells but is insufficient to in-duce invasion in benign cells. DNA Cell Biol 2005; 24(11): 766-76. [CrossRef] google scholar
  • 39. Gusterson BA, Ross DT, Heath VJ, Stein T. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res 2005; 7(4): 1438. [CrossRef] google scholar
  • 40. Sabate JM, Clotet M, Torrubia S, Gomez A, Guerrero R, de las Heras P, et al. Radiologic evaluation of breast disorders related to preg-nancy and lactation Radiographics 2007; 27(Suppl 1): S101-24. [CrossRef] google scholar
  • 41. Shin SJ, Rosen PP. Carcinoma arising from pre-existing pregnan-cy-like and cystic hypersecretory lesions of the breast: a clinico-pathologic study of 9 patients. Am J Surg Pathol 2004; 28: 789-93. [CrossRef] google scholar
  • 42. Amee J. George Ross D. Hannan Walter G. Thomas Unravelling the molecular complexity of GPCR-mediated EGFR transactivation using functional genomics approaches. The FEBS Journal 2013; 280(21): 5258-68. [CrossRef] google scholar
  • 43. Boerner JL, Biscardi JS, Silva CM, Parsons SJ. Transactivating agonists of the EGF receptor require Tyr 845 phosphorylation for induction of DNA synthesis. Mol Carcinog 2005; 44(4): 262-73. [CrossRef] google scholar
  • 44. Joslin EJ, Opresko LK, Wells A, Wiley HS, Lauffenburger DA. EGF-re-ceptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation. J Cell Sci 2007; 120(Pt 20): 3688-99. [CrossRef] google scholar
  • 45. Cramer H, Schmenger K, Heinrich K, Horstmeyer A, Böning H, Breit A, et al. Coupling of endothelin receptors to the ERK/MAP kinase pathway. Roles of palmitoylation and G(alpha)q. Eur J Biochem 2001; 268(20): 5449-59. [CrossRef] google scholar
  • 46. Hua H, Munk S, Whiteside CI. Endothelin-1 activates mesangial cell ERK1/2 via EGF- receptor transactivation and caveolin-1 inte-raction Am J Physiol Renal Physiol 2003; 284(2): F303-12. [Cross-Ref] google scholar
  • 47. Kodama H, Fukuda K, Takahashi T, Sano M, Kato T, Tahara S, et al. Role of EGF Receptor and Pyk2 in endothelin-1-induced ERK acti-vation in rat cardiomyocytes. J Mol Cell Cardiol 2002; 34(2): 13950. [CrossRef] google scholar
  • 48. Chu TS, Wu MS, Wu KD, Hsieh BS. Endothelin-1 activates MAPKs and modulates cell cycle proteins in OKP cells. J Formos Med As-soc 2007; 106(4): 273-80. [CrossRef] google scholar
  • 49. Jackson LF, Qiu TH, Sunnarborg SW, Chang A, Zhang C, Patterson C, et al. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J 2003; 22(11): 2704-16. [CrossRef] google scholar
  • 50. Sternlicht M & Sunnarborg SW. The ADAM17-amphiregulin-EGFR axis in mammary development and cancer. J Mammary Gland Biol Neoplasia 2008; 13(2): 181-94. [CrossRef] google scholar
  • 51. Gilmore JL, Scott JA, Bouizar Z, Robling A, Pitfield SE, Riese DJ, et al. Amphiregulin EGFR Signaling regulates PTHrP gene Expression in Breast cancer cells. Breast Cancer Res Treat 2008; 10(3): 493-505. [CrossRef] google scholar
  • 52. Normanno N, Kim N, Wen D, Smith K, Harris AL, Plowman G, et al. Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor fa-mily, in human breast carcinomas. Breast Cancer Res Treat 1995; 35(3): 293-7. [CrossRef] google scholar
  • 53. Willmarth NE & Ethier SP. Amphiregulin as a novel target for breast cancer therapy. J Mammary Gland Biol Neoplasia 2008; 13(2): 1719. [CrossRef] google scholar
  • 54. Mark DS, Susan WS. The ADAM 17 Amphiregulin EGFR axis in mammary development and Cancer. J Mammary Gland Biol Ne-oplasia 2008; 13: 181-94. [CrossRef] google scholar
  • 55. Gschwind A, Hart S, Fischer OM, Ullrich A. TACE cleavage of pro-amphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J 2003; 22(10): 2411-21. [CrossRef] google scholar
  • 56. Zheng X, Jiang F, Katakowski M, Zhang ZG, Lu QE, Chopp M. ADAM17 promotes breast cancer cell malignant phenotype th-rough EGFR-PI3K-AKT activation. Cancer Biol Ther 2009; 8(11): 1045-54. [CrossRef] google scholar
  • 57. L. Kappes, RL. Amer, S Sommerlatte, G Bashir, C Plattfaut, F Giese-ler, et al. Ambrisentan, an endothelin receptor type A-selective an-tagonist, inhibits cancer cell migration, invasion, and metastasis. Nature Scientific Reports 2020; 10: 15931. [CrossRef] google scholar
  • 58. HM Ahn , DG Kim, YJ Kim. Blockade of endothelin receptor A enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Biochem Biophys Res Commun 2020; 527(2): 568-73. [CrossRef] google scholar

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

Year 2021, Volume: 11 Issue: 1, 1 - 11, 03.05.2021
https://doi.org/10.26650/experimed.2021.864886

Abstract

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 vit-ro çalışmalarda gösterilmiştir. Ayrıca, son dönem in vitro çalışmalar, endotelin-1 (ET-1) sinyal yolağının kanser patofizyolojisi üzerinde-ki ilişkisine odaklanmıştır. Bu bağlamda, ET-1 reseptörleri ve EGFR arasındaki reseptör çapraz etkileşim analizine ve EGFR aktivasyo-nunun fonksiyonel sonuçlarından proliferatif hastalıklara olan ar-tan ilgi, bize bu fenomeni in vivo analiz etme fikrini oluşturmuştur.

Gereç ve Yöntem:ET-1 transgenik fareler ve kontrol fareleri arasın-da geç gebelik dönemi (n=7 ), erken laktasyon dönemi (n=6 ) orta dönem laktasyon (n=10) ve involusyon 14. gün (n=7) sırasında kar-şılaştırmalı bir çalışma gerçekleştirildi. Meme bezlerinden hema-toksilen-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 kulla-nılarak analiz edildi. Bu aktivitelerde önemli bir rol oynadığı bilinen genler (amfiregulin, TGFa, EGF, HB-EGF, ADAM 17), gercek zamanlı po-limeraz zincir reaksiyonu (RT-PCR) teknikleri kullanılarak analiz edildi.

Bulgular:ET-1 transgenik fareler, laktasyon döneminin ortasında hiper-proliferatif lezyonlar (laktasyonel hiperplazi) geliştirdi. RT-PCRanalizlerimiz, transgenik farelerde amfiregulin ve ADAM 17 gen anlatımlarında belirgin bir artış olduğunu göstermektedir. Ayrıca transgenik meme bezlerinde daha yüksek EGFR ve ERKs aktivas-yonları 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 aktivasyonu-nu sağlayarak proliferatif hastalıklarda önemli bir role sahip oldu-ğunu göstermektedir.

References

  • 1. Itoh Y, Kimura C, Onda H, Fujino M. Canine endothelin-2: cDNA sequence for the mature peptide. Nucleic Acids Res 1989; 17(13): 5389. [CrossRef] google scholar
  • 2. Takaoka M, Miyata Y, Takenobu Y, Ikegawa R, Matsumura Y, Mori-moto S. Mode of cleavage of pig big endothelin-1 by chymotry-psin. Production and degradation of mature endothelin-1. Bioc-hem J 1990; 270(2): 541-4. [CrossRef] google scholar
  • 3. Battistini B, D’Orleans-Juste P, Sirois P. Endothelins: circulating plasma levels and presence in other biologic fluids. Lab Invest 1993; 68(6): 600-28. google scholar
  • 4. Moraitis S, Miller WR, Smyth JF, Langdon SP. Paracrine regulation of ovarian cancer by endothelin Eur J Cancer 1999; 35(9): 1381-7. [CrossRef] google scholar
  • 5. Marsault R, Feolde E, Frelin C. Receptor externalization determines sustained contractile responses to endothelin-1 in the rat aorta. Am J Physiol 1993; 264(3 Pt 1): C687-93. [CrossRef] google scholar
  • 6. Yanagisawa M & Masaki T. Endothelin, a novel endothelium-deri-ved peptide. Pharmacological activities, regulation and possible roles in cardiovascular control. Biochem Pharmacol 1989; 38(12): 1877-83. [CrossRef] google scholar
  • 7. Rozengurt E. Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol 2007; 213(3): 589-602. [CrossRef] google scholar
  • 8. Cazaubon SM, Ramos-Morales F, Fischer S, Schweighoffer F, Stros-berg AD, Couraud PO. Endothelin induces tyrosine phosphoryla-tion and Grb2 association of Shc in astrocytes. J Biol Chem 1994; 269: 24805-9. [CrossRef] google scholar
  • 9. Daaka Y. G proteins in cancer: the prostate cancer paradigm. Sci STKE 2004; re2. [CrossRef] google scholar
  • 10. Wiesen JF, Young P, Werb Z, Cunha GR. Signaling through the stro-mal epidermal growth factor receptor is necessary for mammary ductal development. Development 1999; 126: 335-44. google scholar
  • 11. Hynes NE & Watson CJ. Mammary gland growth factors: roles in normal development and in cancer. Cold Spring Harb Perspect Biol 2010; 2(8): a003186. [CrossRef] google scholar
  • 12. Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors. Nature. 1996; 379(6565): 557-60. [CrossRef] google scholar
  • 13. Zhang Q, Thomas SM, Lui VW, Xi S, Siegfried JM, Fan H, et al. Phosphorylation of TNF-alpha converting enzyme by gastrin-re-leasing peptide induces amphiregulin release and EGF receptor activation Proc Natl Acad Sci U S A. 2006; 103(18): 6901-6. google scholar
  • 14. Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci U S A. 2007; 104(13): 5455-60. [CrossRef] google scholar
  • 15. Greco S, Muscella A, Elia MG, Salvatore P, Storelli C, Mazzotta A. Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells. J Cell Physiol 2003; 196: 370-7. [CrossRef] google scholar
  • 16. Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S. PKC-z is required for angiotensin II-induced activation of ERK and synthesis of C-FOS in MCF-7 cells. J Cell Physiol 2003; 197: 61-8. [CrossRef] google scholar
  • 17. Rosano L, Di Castro V, Spinella F, Tortora G, Nicotra MR, Natali PG, et al. Combined targeting of endothelin A receptor and epidermal growth factor receptor in ovarian cancer shows enhanced antitu-mor activity. Cancer Res 2007; 67(13): 6351-9. [CrossRef] google scholar
  • 18. Peles E & Yarden Y. Neu and its ligands: from an oncogene to neu-ral factors. Bioessays 1993; 15: 815-24. [CrossRef] google scholar
  • 19. Cohen S. Nobel lecture. Epidermal growth factor Biosci Rep 1986; 6(12): 1017-28. [CrossRef] google scholar
  • 20. Luetteke NC, Qiu TH, Fenton SE, Troyer KL, Riedel RF, Chang A, et al. Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. Development 1999; 126: 2739-50. google scholar
  • 21. Higashiyama S, Lau K, Besner GE Abraham JA, Klagsbrun M. Stru-cture of heparin-binding EGF-like growth factor. Multiple forms, primary structure, and glycosylation of the mature protein. J Biol Chem 1992; 267(9): 6205-12. [CrossRef] google scholar
  • 22. Shoyab M, McDonald VL, Bradley JG, Todaro GJ. Amphiregulin: a bifunctional growth- modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adeno-carcinoma cell line MCF-7. Proc Natl Acad Sci U.S.A. 1988; 85(17): 6528-32. [CrossRef] google scholar
  • 23. Riese DJ, Komurasaki T, Plowman GD, Stern D. Activation of ErbB4 by the bifunctional epidermal growth factor family hormone epi-regulin is regulated by ErbB2. J Biol Chem 1998; 273(18): 1128894. [CrossRef] google scholar
  • 24. Strachan L, Murison JG, Prestidge RL, Sleeman MA, Watson JD, Kumble KD. Cloning and biological activity of epigen, a novel member of the epidermal growth factor superfamily. J Biol Chem 2001; 276(21): 18265-71. [CrossRef] google scholar
  • 25. Salomon DS, Bianco C, De Santis M. Cripto: a novel epidermal growth factor (EGF)-related peptide in mammary gland develop-ment and neoplasia. Bioessays 1999; 21(1): 61-70. [CrossRef] google scholar
  • 26. Troyer KL & Lee DC. Regulation of mouse mammary gland de-velopment and tumorigenesis by the ERBB signaling network. J Mammary Gland Biol Neoplasia 2001; 6(1): 7-21. google scholar
  • 27. Hocher B, Thöne-Reineke C, Rohmeiss P, Schmager F, Slowinski T, Burst V, et al. Endothelin-1 transgenic mice develop glomerulosc-lerosis, interstitial fibrosis, and renal cysts but not hypertension. J Clin Invest 1997; 99(6): 1380-9. [CrossRef] google scholar
  • 28. Pfaffl MW, Horghan GW, Dempfle L. Relative expression software tool (REST) for group- wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Resear-ch 2002; 30(9): e36. [CrossRef] google scholar
  • 29. Fowler, KJ, Walker F, Alexander W, Hibbs ML, Nice EC, Bohmer RM, et al. A mutation in the epidermal growth factor receptor in wa-ved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation. Proc Natl Acad Sci USA 1995; 92: 1465-9. [CrossRef] google scholar
  • 30. Xie W, Paterson AJ, Chin E, Nabell LM, Kudlow JE. Targeted exp-ression of a dominant negative epidermal growth factor recep-tor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol 1997; 11: 1766-81. [CrossRef] google scholar
  • 31. Tsujioka H, Yotsumoto F, Shirota K, Horiuchi S, Yoshizato T, Kuroki M, et al. Emerging strategies for ErbB ligand-based targeted the-rapy for cancer. Anticancer Res 2010; 30(8): 3107-12. google scholar
  • 32. D’Cruz CM, Moody SE, Master SR, Hartman JL, Keiper EA, Imielins-ki MB, et al. Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland. Mol Endocrinol 2002; 16(9): 2034-51. [CrossRef] google scholar
  • 33. Schroeder JA & Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ 1998; 9: 451-64. google scholar
  • 34. Bagnato A, Tecce R, Di Castro V, Catt KJ. Activation of mitogenic signaling by endothelin 1 in ovarian carcinoma cells. Cancer Res 1997; 57(7): 1306-11. google scholar
  • 35. Alanen K, Deng DX, Chakrabarti S. Augmented expression of en-dothelin-1, endothelin-3 And the endothelin-B receptor in breast carcinoma. Histopathology 2000; 36(2): 161-7. [CrossRef] google scholar
  • 36. Bagnato A, Rosano L, Di Castro V, Albini A, Salani D, Varmi M, et al. Endothelin receptor blockade inhibits proliferation of Kaposi’s sarcoma cells. Am J Pathol 2001; 158(3): 841-7. [CrossRef] google scholar
  • 37. Nelson J, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer 2003; 3(2): 110-6. [CrossRef] google scholar
  • 38. Hagemann T, Binder C, Binder L, Pukrop T, Trumper L, Grimshaw, MJ. Expression of endothelins and their receptors promotes an invasive Phenotype of breast tumor cells but is insufficient to in-duce invasion in benign cells. DNA Cell Biol 2005; 24(11): 766-76. [CrossRef] google scholar
  • 39. Gusterson BA, Ross DT, Heath VJ, Stein T. Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res 2005; 7(4): 1438. [CrossRef] google scholar
  • 40. Sabate JM, Clotet M, Torrubia S, Gomez A, Guerrero R, de las Heras P, et al. Radiologic evaluation of breast disorders related to preg-nancy and lactation Radiographics 2007; 27(Suppl 1): S101-24. [CrossRef] google scholar
  • 41. Shin SJ, Rosen PP. Carcinoma arising from pre-existing pregnan-cy-like and cystic hypersecretory lesions of the breast: a clinico-pathologic study of 9 patients. Am J Surg Pathol 2004; 28: 789-93. [CrossRef] google scholar
  • 42. Amee J. George Ross D. Hannan Walter G. Thomas Unravelling the molecular complexity of GPCR-mediated EGFR transactivation using functional genomics approaches. The FEBS Journal 2013; 280(21): 5258-68. [CrossRef] google scholar
  • 43. Boerner JL, Biscardi JS, Silva CM, Parsons SJ. Transactivating agonists of the EGF receptor require Tyr 845 phosphorylation for induction of DNA synthesis. Mol Carcinog 2005; 44(4): 262-73. [CrossRef] google scholar
  • 44. Joslin EJ, Opresko LK, Wells A, Wiley HS, Lauffenburger DA. EGF-re-ceptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation. J Cell Sci 2007; 120(Pt 20): 3688-99. [CrossRef] google scholar
  • 45. Cramer H, Schmenger K, Heinrich K, Horstmeyer A, Böning H, Breit A, et al. Coupling of endothelin receptors to the ERK/MAP kinase pathway. Roles of palmitoylation and G(alpha)q. Eur J Biochem 2001; 268(20): 5449-59. [CrossRef] google scholar
  • 46. Hua H, Munk S, Whiteside CI. Endothelin-1 activates mesangial cell ERK1/2 via EGF- receptor transactivation and caveolin-1 inte-raction Am J Physiol Renal Physiol 2003; 284(2): F303-12. [Cross-Ref] google scholar
  • 47. Kodama H, Fukuda K, Takahashi T, Sano M, Kato T, Tahara S, et al. Role of EGF Receptor and Pyk2 in endothelin-1-induced ERK acti-vation in rat cardiomyocytes. J Mol Cell Cardiol 2002; 34(2): 13950. [CrossRef] google scholar
  • 48. Chu TS, Wu MS, Wu KD, Hsieh BS. Endothelin-1 activates MAPKs and modulates cell cycle proteins in OKP cells. J Formos Med As-soc 2007; 106(4): 273-80. [CrossRef] google scholar
  • 49. Jackson LF, Qiu TH, Sunnarborg SW, Chang A, Zhang C, Patterson C, et al. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. EMBO J 2003; 22(11): 2704-16. [CrossRef] google scholar
  • 50. Sternlicht M & Sunnarborg SW. The ADAM17-amphiregulin-EGFR axis in mammary development and cancer. J Mammary Gland Biol Neoplasia 2008; 13(2): 181-94. [CrossRef] google scholar
  • 51. Gilmore JL, Scott JA, Bouizar Z, Robling A, Pitfield SE, Riese DJ, et al. Amphiregulin EGFR Signaling regulates PTHrP gene Expression in Breast cancer cells. Breast Cancer Res Treat 2008; 10(3): 493-505. [CrossRef] google scholar
  • 52. Normanno N, Kim N, Wen D, Smith K, Harris AL, Plowman G, et al. Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor fa-mily, in human breast carcinomas. Breast Cancer Res Treat 1995; 35(3): 293-7. [CrossRef] google scholar
  • 53. Willmarth NE & Ethier SP. Amphiregulin as a novel target for breast cancer therapy. J Mammary Gland Biol Neoplasia 2008; 13(2): 1719. [CrossRef] google scholar
  • 54. Mark DS, Susan WS. The ADAM 17 Amphiregulin EGFR axis in mammary development and Cancer. J Mammary Gland Biol Ne-oplasia 2008; 13: 181-94. [CrossRef] google scholar
  • 55. Gschwind A, Hart S, Fischer OM, Ullrich A. TACE cleavage of pro-amphiregulin regulates GPCR-induced proliferation and motility of cancer cells. EMBO J 2003; 22(10): 2411-21. [CrossRef] google scholar
  • 56. Zheng X, Jiang F, Katakowski M, Zhang ZG, Lu QE, Chopp M. ADAM17 promotes breast cancer cell malignant phenotype th-rough EGFR-PI3K-AKT activation. Cancer Biol Ther 2009; 8(11): 1045-54. [CrossRef] google scholar
  • 57. L. Kappes, RL. Amer, S Sommerlatte, G Bashir, C Plattfaut, F Giese-ler, et al. Ambrisentan, an endothelin receptor type A-selective an-tagonist, inhibits cancer cell migration, invasion, and metastasis. Nature Scientific Reports 2020; 10: 15931. [CrossRef] google scholar
  • 58. HM Ahn , DG Kim, YJ Kim. Blockade of endothelin receptor A enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Biochem Biophys Res Commun 2020; 527(2): 568-73. [CrossRef] google scholar
There are 58 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Nadir Gül 0000-0003-1259-4910

Franz Theuring This is me 0000-0003-1736-0312

Publication Date May 3, 2021
Submission Date January 19, 2021
Published in Issue Year 2021 Volume: 11 Issue: 1

Cite

Vancouver 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.