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.
Balamurugan, K