Prostate-specific membrane antigen associates with anaphase-promoting complex and induces chromosomal instability

Mol Cancer Ther. 2008 Jul;7(7):2142-51. doi: 10.1158/1535-7163.MCT-08-0005.


Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in advanced and metastatic prostate cancers. The pathologic consequence of elevated PSMA expression in not known. Here, we report that PSMA is localized to a membrane compartment in the vicinity of mitotic spindle poles and associates with the anaphase-promoting complex (APC). PSMA-expressing cells prematurely degrade cyclin B and exit mitosis due to increased APC activity and incomplete inactivation of APC by the spindle assembly checkpoint. Further, expression of PSMA in a karyotypically stable cell line induces aneuploidy. Thus, these findings provide the first evidence that PSMA has a causal role in the induction of aneuploidy and might play an etiologic role in the progression of prostate cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Centrosome / drug effects
  • Centrosome / ultrastructure
  • Chromosomal Instability* / drug effects
  • Cyclin B / metabolism
  • Cyclin B1
  • Dogs
  • Humans
  • Nocodazole / pharmacology
  • Prostate-Specific Antigen / metabolism*
  • Prostate-Specific Antigen / ultrastructure
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Spindle Apparatus / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism*


  • CCNB1 protein, human
  • Cyclin B
  • Cyclin B1
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Prostate-Specific Antigen
  • Nocodazole