Tumour-suppression activity of the proapoptotic regulator Par4. Academic Article uri icon

Overview

abstract

  • The proapoptotic protein encoded by Par4 (prostate apoptosis response 4) has been implicated in tumour suppression, particularly in the prostate. We report here that Par4-null mice are prone to develop tumours, both spontaneously and on carcinogenic treatment. The endometrium and prostate of Par4-null mice were particularly sensitive to the development of proliferative lesions. Most (80%) Par4-null females presented endometrial hyperplasia by 9 months of age, and a significant proportion (36%) developed endometrial adenocarcinomas after 1 year of age. Similarly, Par4-null males showed a high incidence of prostate hyperplasia and prostatic intraepithelial neoplasias, and were extraordinarily sensitive to testosterone-induced prostate hyperplasia. Finally, the uterus and prostate of young Par4-null mice have increased levels of the apoptosis inhibitor XIAP (X-chromosome-linked inhibitor of apoptosis), supporting the previously proposed function of Par4 as an inhibitor of the (zeta)PKC (atypical protein kinase)-NF-(kappa)B (nuclear factor-(kappa)B)-XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate.

publication date

  • June 1, 2005

Research

keywords

  • Apoptosis
  • Endometrial Neoplasms
  • Phenotype
  • Prostatic Neoplasms
  • Proteins
  • Receptors, Thrombin
  • Urinary Bladder Neoplasms

Identity

PubMed Central ID

  • PMC1369092

Scopus Document Identifier

  • 22144496103

Digital Object Identifier (DOI)

  • 10.1038/sj.embor.7400421

PubMed ID

  • 15877079

Additional Document Info

volume

  • 6

issue

  • 6