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Cerebellar Degeneration-Related Protein 2 (CDR2): Cell-Cycle Regulated Tumor Antigen

Wed, 12/05/2012 - 10:23


CDR2 is a tumor antigen expressed in a high percentage of breast and ovarian tumors and is the target of a naturally occurring tumor immune response in patients with paraneoplastic cerebellar degeneration. CDR2 has also been shown to be a cell cycle regulated protein in tumor cells with protein levels peaking in mitosis (1). Loss of CDR2 in cells has been linked to aberrant mitotic spindle formation and impaired proliferation. Conversely, CDR2 overexpression is also responsible for cell proliferation in tumors.

Western Blot: CDR2 Antibody (33)

Neoplastic expression of CDR2 in ovary and breast tumors  has been shown to trigger an autoimmune response that suppresses tumor growth by developing tumor immunity, but culminates in cerebellar degeneration when CDR2-specific immune cells recognize neuronal CDR2 (2). CDR2 protein has been shown to be present in 62% of ovarian cancers, but not in normal ovary tissue. The biological function of CDR2 is partly characterized, as CDR2 through its leucine zipper motif has been demonstrated to interact with c-myc (3). CDR2 was expressed with higher intensity in ovarian, than in lung cancer cells as demonstrated by Western blots and  using anti-CDR2 antibodies, but immunofluorescence studies of ovarian, cervical, and lung cancer cell lines revealed approximately similar CDR2 granular staining which was mainly localized to the cytoplasm (4). Taken together, these observations indicate that the onconeural antigen CDR2 acts during mitosis, at least in part through interactions with c-myc, to regulate a cascade of actions that may present new targeting opportunities in gynecological cancers.

 

  1. PMID: 20383333
  2. PMID: 19581925
  3. PMID: 10465786
  4. PMID: 21080165

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