MYCN and survivin cooperatively contribute to malignant transformation of fibroblasts.

Abstract	The oncogenes MYCN and survivin (BIRC5) maintain aggressiveness of diverse cancers including sarcomas. To investigate whether these oncogenes cooperate in initial malignant transformation, we transduced them into Rat-1 fibroblasts. Indeed, survivin enhanced MYCN-driven contact-uninhibited and anchorage-independent growth in vitro. Importantly, upon subcutaneous transplantation into mice, cells overexpressing both instead of either one of the oncogenes generated tumors with shortened latency, marked anaplasia and an increased proliferation-to-apoptosis ratio resulting in accelerated growth. Mechanistically, the increased tumorigenicity was associated with an enhanced Warburg effect and a hypoxia inducible factor 1α linked vascular remodeling. This cooperation between MYCN and survivin may be important in the genesis of several cancers.
Authors	Nora I Hipp, Lisa Christner, Thomas Wirth, Wolfgang Mueller-Klieser, Stefan Walenta, Evelin Schröck, Klaus-Michael Debatin, Christian Beltinger
Journal	Carcinogenesis (Carcinogenesis) Vol. 35 Issue 2 Pg. 479-88 (Feb 2014) ISSN: 1460-2180 [Electronic] England
PMID	24130166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	BIRC5 protein, human Homeodomain Proteins Inhibitor of Apoptosis Proteins MYCN protein, human N-Myc Proto-Oncogene Protein Nuclear Proteins Oncogene Proteins RNA, Messenger Survivin RAG-1 protein Lactic Acid Adenosine Triphosphate Glucose
Topics	Adenosine Triphosphate (metabolism) Animals Apoptosis Blotting, Western Cell Hypoxia Cell Proliferation Cell Transformation, Neoplastic (metabolism, pathology) Cells, Cultured Fibroblasts (metabolism, pathology) Glucose (metabolism) Glycolysis Homeodomain Proteins (physiology) Humans Immunoenzyme Techniques Inhibitor of Apoptosis Proteins (genetics, metabolism) Lactic Acid (metabolism) Mice N-Myc Proto-Oncogene Protein Nuclear Proteins (genetics, metabolism) Oncogene Proteins (genetics, metabolism) RNA, Messenger (genetics) Rats Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Survivin

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