Advertisement

Cytotechnology

, Volume 71, Issue 1, pp 209–217 | Cite as

Vitronectin, fibronectin and epidermal growth factor induce proliferation via the JNK and ERK pathways in insulinoma INS-1 cells

  • Ayse Karatug KacarEmail author
  • Sehnaz Bolkent
Article
  • 62 Downloads

Abstract

An insulinoma is a tumor formed by beta cells in the Langerhans islets of the pancreas. Vitronectin (VTN), fibronectin (FN) and epidermal growth factor (EGF) are important in cell signaling. The aim of this study was to investigate the molecular mechanism that occurs in INS-1 cells with the administration of VTN, FN and EGF in proliferative doses. We determined the proliferative doses of EGF, VTN and FN. The molecular mechanism of proliferation has been investigated alone or in the combination of these proteins. It was observed that INS-1 cells did not have VTN and FN. Cell viability increased with the administration of 0.1 μg/ml VTN, 0.1 μg/ml FN and 1 mg/ml EGF. Proliferation increased with the administration of FN + EGF, and VTN + FN + EGF together when compared to the control group. The total JNK levels did not change between the groups; however, the active JNK levels increased in the VT + FN + EGF group compared to the control group. The total ERK levels increased in the VT + FN + EGF group, and the active ERK levels increased in the VTN + FN, VTN + EGF and VTN + FN + EGF groups compared to the control group. The JNK and ERK pathways are important for proliferation. The JNK and ERK pathways were activated in VTN + FN + EGF administered group. However, it was observed that the ERK pathway was more active than the JNK pathway.

Keywords

Insulinoma INS-1 cells Vitronectin Fibronectin Epidermal growth factor JNK/ERK pathways 

Notes

Acknowledgements

Thank to Prof. Dr. Claes B. Wollheim (University Medical Center, Geneva) for providing kind gift of insulinoma INS-1 cell lines. This study was supported by the Research Fund of Istanbul University. Project Nos.: 14831 and UDP-56108.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Adjei AA (2005) The role of mitogen-activated ERK kinase inhibitors in lung cancer therapy. Clin Lung Cancer 7:221–223CrossRefGoogle Scholar
  2. Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410:37–40CrossRefGoogle Scholar
  3. Correia CR, Gaifem J, Oliveira MB, Silvestre R, Mano JF (2017) The influence of surface modified poly(l-lactic acid) films on the differentiation of human monocytes into macrophages. Biomater Sci 5:551–560CrossRefGoogle Scholar
  4. Davis RJ (2000) Signal transduction by the JNK group of MAP kinases. Cell 103:239–252CrossRefGoogle Scholar
  5. De Bono JS, Rowinsky EK (2002) Therapeutics targeting signal transduction for patients with colorectal carcinoma. Br Med Bull 64:227–254CrossRefGoogle Scholar
  6. De Luca A, Maiello MR, D’Alessio A, Pergameno M, Normanno N (2012) The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets 16:S17–S27CrossRefGoogle Scholar
  7. Ellenrieder V, Adler G, Gress TM (1999) Invasion and metastasis in pancreatic cancer. Ann Oncol 10:46Y50CrossRefGoogle Scholar
  8. George EL, Georges-Labouesse EN, Patel-King RS, Rayburn H, Hynes R (1993) Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development 119:1079–1091Google Scholar
  9. Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285:1028–1033CrossRefGoogle Scholar
  10. Grassian AR, Metallo CM, Coloff JL, Stephanopoulos G, Brugge JS (2011) Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation. Genes Dev 25:1716–1733CrossRefGoogle Scholar
  11. Han J, Ulevitch RJ (1999) Emerging targets for anti-inflammatory therapy. Nat Cell Biol 1:E39–E40CrossRefGoogle Scholar
  12. Hess S, Kanse SM, Kost C, Preissner KT (1995) The versatility of adhesion receptor ligands in haemostasis: morpho-regulatory functions of vitronectin. Thromb Haemost 74:258–265Google Scholar
  13. Huang X, Wu J, Spong S, Sheppard D (1998) The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin. J Cell Sci 111:2189–2195Google Scholar
  14. Hynes RO (1987) Integrins: a family of cell surface receptors. Cell 48:549–554CrossRefGoogle Scholar
  15. Janjic D, Wollheim CB (1992) Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay. Diabetologia 35:482–485CrossRefGoogle Scholar
  16. Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298:1911–1912CrossRefGoogle Scholar
  17. Karatug Kacar A, Bolkent S (2018) Necrotic cell death occur via JNK pathway with the activity of transcription factor c-Jun by 4-MC in INS-1 cell line. J Cell Biochem 119:2048–2060CrossRefGoogle Scholar
  18. Kawahara E, Nakada N, Hikichi T, Kobayashi J, Nakanishi I (2002) EGF and beta1 integrin convergently regulate migration of A431 carcinoma cell through MAP kinase activation. Exp Cell Res 272:84–91CrossRefGoogle Scholar
  19. Lubinus M, Meier KE, Smith EA, Gause KC, LeRoy EC, Trojanowska M (1994) Independent effects of platelet-derived growth factor isoforms on mitogen-activated protein kinase activation and mitogenesis in human dermal fibroblasts. J Biol Chem 269:9822–9825Google Scholar
  20. Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, Derynck R (1995) Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 376:337–341CrossRefGoogle Scholar
  21. Miettinen PJ, Huotari M, Koivisto T, Ustinov J, Palgi J, Rasilainen S, Lehtonen E, Keski-Oja J, Otonkoski T (2000) Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development 127:2617–2627Google Scholar
  22. Moreno-Layseca P, Streuli CH (2014) Signalling pathways linking integrins with cell cycle progression. Matrix Biol 34:144–153CrossRefGoogle Scholar
  23. Nielsen JH (1989) Mechanisms of pancreatic beta-cell growth and regeneration: studies on rat insulinoma cells. Exp Clin Endocrinol 93:277–285CrossRefGoogle Scholar
  24. Ono K, Han J (2000) The p38 signal transduction pathway: activation and function. Cell Signal 12:1–13CrossRefGoogle Scholar
  25. Podor TJ, Campbell S, Chindemi P, Foulon DM, Farrell DH, Walton PD et al (2002) Incorporation of vitronectin into fibrin clots. Evidence for a binding interaction between vitronectin and gamma A/gamma’ fibrinogen. J Biol Chem 277:7520–7528CrossRefGoogle Scholar
  26. Poitout V, Olson LK, Robertson RP (1996) Insulin-secreting cell lines: classification, characteristics and potential applications. Diabetes Metab 22:7–14Google Scholar
  27. Robinson MJ, Cobb MH (1997) Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9:180–186CrossRefGoogle Scholar
  28. Roy SK, Srivastava RK, Shankar S (2010) Inhibition of PI3K/AKT and MAPK/ERK pathways causes activation of FOXO transcription factor, leading to cell cycle arrest and apoptosis in pancreatic cancer. J Mol Signal 5:10CrossRefGoogle Scholar
  29. Santen RJ, Song RX, McPherson R, Kumar R, Adam L, Jeng MH, Yue W (2002) The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol 80:239–256CrossRefGoogle Scholar
  30. Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435–2444CrossRefGoogle Scholar
  31. Schvartz I, Seger D, Shaltiel S (1999) Vitronectin. Int J Biochem Cell Biol 31:539–544CrossRefGoogle Scholar
  32. Seiffert D, Crain K, Wagner NV, Loskutoff DJ (1994) Vitronectin gene expression in vivo. Evidence for extrahepatic synthesis and acute phase regulation. J Biol Chem 269:19836–19842Google Scholar
  33. Sibilia M, Wagner EF (1995) Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 269:234–238CrossRefGoogle Scholar
  34. Singh B, Su YC, Riesbeck K (2010) Vitronectin in bacterial pathogenesis: a host protein used in complement escape and cellular invasion. Mol Microbiol 78:545–560CrossRefGoogle Scholar
  35. Sjöholm A (1995) Regulation of insulinoma cell proliferation and insulin accumulation by peptides and second messengers. Upsala J Med Sci 100:201–216CrossRefGoogle Scholar
  36. Skelin M, Rupnik M, Cencic A (2010) Pancreatic beta cell lines and their applications in diabetes mellitus research. Altex 27:105–113CrossRefGoogle Scholar
  37. Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, LaMantia C, Mourton T, Herrup K, Harris RC et al (1995) Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 269:230–234CrossRefGoogle Scholar
  38. Wang Z, Wang M, Carr BI (2008) Integrin alpha5-induced EGFR activation by prothrombin triggers hepatocyte apoptosis via the JNK signaling pathway. J Cell Physiol 216:551–557CrossRefGoogle Scholar
  39. Wang H, Gambosova K, Cooper ZA, Holloway MP, Kassai A, Izquierdo D, Cleveland K, Boney CM, Altura RA (2010) EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells. BMC Mol Biol 11:66CrossRefGoogle Scholar
  40. Wilkins-Port CE, McKeown-Longo PJ (1998) Degradation of distinct forms of multimeric vitronectin by human fibroblasts. Biochim Biophys Acta 1404:353–366CrossRefGoogle Scholar
  41. Wu S, Wells A, Griffith LG, Lauffenburger DA (2011) Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling. Biomaterials 32:7524–7531CrossRefGoogle Scholar
  42. Zheng X, Saunders TL, Camper SA, Samuelson LC, Ginsburg D (1995) Vitronectin is not essential for normal mammalian development and fertility. Proc Natl Acad Sci U S A 92:12426–12430CrossRefGoogle Scholar
  43. Zhuang P, Chen AI, Peterson CB (1997) Native and multimeric vitronectin exhibit similar affinity for heparin. Differences in heparin binding properties induced upon denaturation are due to self-association into a multivalent form. J Biol Chem 272:6858–6867CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceIstanbul UniversityIstanbulTurkey

Personalised recommendations