HER-2/neu-mediated down-regulation of biglycan associated with altered growth properties.

The Journal of Biological Chemistry
Christian V RecktenwaldBarbara Seliger

Abstract

The extracellular matrix protein biglycan (Bgn) is a leucine-rich proteoglycan that is involved in the matrix assembly, cellular migration and adhesion, cell growth, and apoptosis. Although a distinct expression of Bgn was found in a number of human tumors, the role of this protein in the initiation and/or maintenance of neoplastic transformation has not been studied in detail. Using an in vitro model of oncogenic transformation, a down-regulation of Bgn expression as well as an altered secretion of different Bgn isoforms was found both in murine and human HER-2/neu oncogene-transformed cells when compared with HER-2/neu(-) cells. This was associated with a reduced growth, wound closure, and migration capacity. Vice versa, silencing of Bgn in HER-2/neu(-) fibroblasts increased the growth rate and migration capacity of these cells. Bgn expression was neither modulated in HER-2/neu(+) cells by transforming growth factor-β(1) nor by inhibition of the phosphoinositol 3-kinase and MAP kinase pathways. In contrast, inhibition of the protein kinase C (PKC) pathway led to the reconstitution of Bgn expression. In particular, the PKC target protein cAMP response element binding protein (CREB) is a major regulator of Bgn expression as the...Continue Reading

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Citations

Nov 14, 2013·PloS One·Christian NiedworokJens W Fischer
Feb 11, 2014·Biochimica Et Biophysica Acta·Madalina V NastaseLiliana Schaefer
Jul 16, 2013·Matrix Biology : Journal of the International Society for Matrix Biology·Mujib UllahJochen Ringe
Jul 16, 2015·Biochemistry·Thomas NeillRenato V Iozzo
Apr 2, 2015·Biochimica Et Biophysica Acta·Achilleas D TheocharisNikos K Karamanos
Jun 11, 2014·Experimental Biology and Medicine·Ewa M KoźmaKrystyna Olczyk
Sep 17, 2014·The Journal of Biological Chemistry·Tameka A BaileyHamid Band
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Apr 11, 2018·Oncoimmunology·Karthikeyan SubbarayanBarbara Seliger
Aug 4, 2019·Cancer Immunology, Immunotherapy : CII·Michael FriedrichBarbara Seliger
Sep 13, 2013·Molecular Cancer Research : MCR·André StevenBarbara Seliger

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