Universität zu Köln

Walter, Robert Fred Henry, Werner, Robert, Ting, Saskia ORCID: 0000-0003-1415-7714, Vollbrecht, Claudia ORCID: 0000-0002-0861-001X, Theegarten, Dirk, Christoph, Daniel Christian, Schmid, Kurt Werner, Wohlschlaeger, Jeremias and Mairinger, Fabian Dominik (2015). Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis. Oncotarget, 6 (28). S. 24690 - 24699. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Background: Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Materials and Methods: Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. Results: ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Conclusion: Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walter, Robert Fred Henry UNSPECIFIED UNSPECIFIED UNSPECIFIED Werner, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Ting, Saskia UNSPECIFIED orcid.org/0000-0003-1415-7714 UNSPECIFIED Vollbrecht, Claudia UNSPECIFIED orcid.org/0000-0002-0861-001X UNSPECIFIED Theegarten, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Christoph, Daniel Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Kurt Werner UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlschlaeger, Jeremias UNSPECIFIED UNSPECIFIED UNSPECIFIED Mairinger, Fabian Dominik UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-392741
DOI:	10.18632/oncotarget.3992
Journal or Publication Title:	Oncotarget
Volume:	6
Number:	28
Page Range:	S. 24690 - 24699
Date:	2015
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE-EXPRESSION; MESSENGER-RNA; THERAPEUTIC RESPONSE; PULMONARY CARCINOIDS; CANCER-THERAPY; ASSOCIATION; INHIBITION; SURVIVAL; PROTEIN; DISRUPTION Multiple languages Oncology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39274