Keratoepithelin reverts the suppression of tissue factor pathway inhibitor 2 by MYCN in human neuroblastoma: a mechanism to inhibit invasion.

Abstract	Neuroblastoma is the most frequent solid malignancy of children. The most reliable prognostic factor in neuroblastoma is the amplification status of the MYCN oncogene, but exceptions from this rule have been observed. Recently we have demonstrated that keratoepithelin (BIGH3, TGFBI) expression significantly reduces proliferation and invasion of neuroblastomas in vitro and in vivo. In these experiments, we also observed that tissue factor pathway inhibitor 2 (TFPI2, PP5, MSPI), a potent inhibitor of matrix-metalloproteinases, is most prominently up-regulated. As MYCN-amplified neuroblastomas are highly invasive, we sought to determine the interaction between MYCN, keratoepithelin and TFPI2. In this study we provide initial evidence that i) keratoepithelin expression in neuroblastoma inversely correlates with MYCN expression; ii) TFPI2 expression in neuroblastoma also correlates inversely with MYCN expression but positively with keratoepithelin expression and iii) keratoepithelin induces elevated TFPI2 transcript levels in neuroblastoma cells without alterations of MYCN expression.
Authors	Juergen Becker, Sonja Volland, Ievgeniia Noskova, Alexander Schramm, Lothar L Schweigerer, Joerg Wilting
Journal	International journal of oncology (Int J Oncol) Vol. 32 Issue 1 Pg. 235-40 (Jan 2008) ISSN: 1019-6439 [Print] Greece
PMID	18097563 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Extracellular Matrix Proteins Glycoproteins MYCN protein, human N-Myc Proto-Oncogene Protein Nuclear Proteins Oncogene Proteins Transforming Growth Factor beta tissue-factor-pathway inhibitor 2 betaIG-H3 protein
Topics	Cell Line, Tumor Extracellular Matrix Proteins (physiology) Gene Amplification Glycoproteins (genetics, physiology) Humans N-Myc Proto-Oncogene Protein Neoplasm Invasiveness Neuroblastoma (pathology) Nuclear Proteins (genetics, physiology) Oncogene Proteins (genetics, physiology) Oncogenes Transforming Growth Factor beta (physiology)

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