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Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response


Balamurugan, K; Luu, V D; Kaufmann, M R; Hofmann, V S; Boysen, G; Barth, S; Bordoli, M R; Stiehl, D P; Moch, H; Schraml, P; Wenger, R H; Camenisch, G (2009). Onconeuronal cerebellar degeneration-related antigen, Cdr2, is strongly expressed in papillary renal cell carcinoma and leads to attenuated hypoxic response. Oncogene:1-12.

Abstract

The onconeuronal cerebellar degeneration-related
antigen Cdr2 is associated withparaneo plastic syndromes.
Neoplastic expression of Cdr2 in ovary and breast tumors
triggers an autoimmune response that suppresses tumor
growthby developing tumor immunity, but culminates in
cerebellar degeneration when Cdr2-specific immune cells
recognize neuronal Cdr2. We identified Cdr2 as a novel
interactor of the hypoxia-inducible factor (HIF) prolyl-4-
hydroxylase PHD1 and provide evidence that Cdr2 might
represent a novel important tumor antigen in renal cancer.
Strong Cdr2 protein expression was observed in 54.2% of
papillary renal cell carcinoma (pRCC) compared with
7.8% of clear-cell RCC and no staining was observed in
chromophobe RCC or oncocytoma. High Cdr2 protein
levels correlated withattenuate d HIF target gene expression
in these solid tumors, and Cdr2 overexpression in
tumor cell lines reduced HIF-dependent transcriptional
regulation. This effect was because of both attenuation of
hypoxic protein accumulation and suppression of the
transactivation activity of HIF-1a. pRCC is known for its
tendency to avascularity, usually associated witha lower
pathological stage and higher survival rates. We provide
evidence that Cdr2 protein strongly accumulates in pRCC,
attenuates the HIF response to tumor hypoxia and may
become of diagnostic importance as novel renal tumor
marker.

Abstract

The onconeuronal cerebellar degeneration-related
antigen Cdr2 is associated withparaneo plastic syndromes.
Neoplastic expression of Cdr2 in ovary and breast tumors
triggers an autoimmune response that suppresses tumor
growthby developing tumor immunity, but culminates in
cerebellar degeneration when Cdr2-specific immune cells
recognize neuronal Cdr2. We identified Cdr2 as a novel
interactor of the hypoxia-inducible factor (HIF) prolyl-4-
hydroxylase PHD1 and provide evidence that Cdr2 might
represent a novel important tumor antigen in renal cancer.
Strong Cdr2 protein expression was observed in 54.2% of
papillary renal cell carcinoma (pRCC) compared with
7.8% of clear-cell RCC and no staining was observed in
chromophobe RCC or oncocytoma. High Cdr2 protein
levels correlated withattenuate d HIF target gene expression
in these solid tumors, and Cdr2 overexpression in
tumor cell lines reduced HIF-dependent transcriptional
regulation. This effect was because of both attenuation of
hypoxic protein accumulation and suppression of the
transactivation activity of HIF-1a. pRCC is known for its
tendency to avascularity, usually associated witha lower
pathological stage and higher survival rates. We provide
evidence that Cdr2 protein strongly accumulates in pRCC,
attenuates the HIF response to tumor hypoxia and may
become of diagnostic importance as novel renal tumor
marker.

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12 citations in Web of Science®
12 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:19 May 2009
Deposited On:10 Jul 2009 15:49
Last Modified:05 Apr 2016 13:17
Publisher:Nature Publishing Group
ISSN:0950-9232
Funders:Swiss National Foundation, Edoardo R., Giovanni, Giuseppe und Charina Sassella-Stiftung, Zürich, Krebsliga des Kantons Zürich, UZH Univ. Res. Priority Program "Integrative Human Physiology", 6th Framework Programme of the European Commission EUROXY
Publisher DOI:https://doi.org/10.1038/onc.2009.186
Official URL:http://www.nature.com/ajg/journal/vaop/ncurrent/index.html

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