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RAP80/UIMC1 as cancer-associated antigen: alternative splice variants and their immunogenicity

Yuriy V Shebzukhov1, Ekaterina P Koroleva, Svetlana V Khlgatian

  • 1Department of Molecular Immunology, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobjovy Gory, Moscow 119899, Russia.

Cancer Letters
|June 15, 2007
PubMed

Insights

Researchers identified RAP80/UIMC1 as a novel cancer antigen. Autoreactivity to this protein in cancer patients stems from common splice forms, not tumor-specific expression.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • RAP80/UIMC1 is a protein highly expressed in the testis.
  • Antibodies against RAP80/UIMC1 are found in 5-10% of cancer patients.
  • The immunogenicity of RAP80/UIMC1 in cancer warrants investigation.

Purpose of the Study:

  • To investigate the reasons behind RAP80/UIMC1 immunogenicity in cancer patients.
  • To characterize RAP80/UIMC1 splice isoforms.
  • To map the immunogenic regions of RAP80/UIMC1.

Main Methods:

  • Analysis of RAP80/UIMC1 splice isoforms.
  • Mapping of immunogenic protein regions.
  • Transcript expression analysis in normal and tumor tissues.

Main Results:

  • RAP80/UIMC1 transcripts are widely detected in normal tissues and colon tumors.
  • No elevated expression of testis-predominant RAP80/UIMC1 isoforms was observed in tumors from seropositive patients.
  • The primary immunogenic region of RAP80/UIMC1 is located in the central part, encoded by exon 9, present in ubiquitous splice forms.

Conclusions:

  • Autoreactivity to RAP80/UIMC1 in cancer patients is not due to overexpression or tumor-specific splicing.
  • The immunogenicity is linked to common splice variants containing the immunogenic exon 9.
  • Further research is needed to elucidate the precise mechanisms driving RAP80/UIMC1 autoimmunity in cancer.

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