Characterization of SPINK1 in Prostate Cancer

Abstract

In cancer, specific growth and invasion-promoting proteins are abnormally over-expressed compared to normal cells and these proteins are often the target of therapies designed to inactivate them. The computational methods developed by our lab was used to identify highly over-expressed genes specifically in cancer cells, a method that was instrumental in identifying the first gene fusion in the majority of prostate cancer, TMPRSS-ETS. Utilizing the same method, the gene SPINK1 was later identified as highly over-expressed in prostate cancer, specifically in prostate cancer patients that were negative for the TMPRSS-ETS gene fusions. An antibody that targets the SPINK1 protein was tested in pre-clinical models for its potential as effective therapy to treat TMPRSS-ETS-negative prostate cancer. Here, an antibody against the SPINK1 protein was used to examine its effects on various prostate cancer cell lines. The anti-SPINK1 antibody was able to inhibit the growth of cells that over-expressed SPINK1 but had no effect on cells that harbored other aberrations. Importantly, the anti-SPINK1 antibody also significantly halted the tumor growth in mice that were implanted with SPINK1 over-expressing tumors. These results suggest that a sub-set of TMPRSS-ETS negative prostate cancer patients that over-express SPINK1 can potentially be successfully treated with anti-SPINK1 antibody.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
May 01, 2011
Accession Number
ADA549045

Entities

People

  • Arul Chinnaiyan

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Movement
  • Cells
  • Chemistry
  • Computational Science
  • Culture Media
  • Department Of Defense
  • Enzyme Inhibitors
  • Genetics
  • Membranes
  • Neoplasms
  • Polymerase Chain Reaction
  • Prostate Cancer
  • Proteins
  • Therapy

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Oncology (Cancer Research).