Title | Tumour-suppression activity of the proapoptotic regulator Par4. |
Publication Type | Journal Article |
Year of Publication | 2005 |
Authors | Garcia-Cao I, Duran A, Collado M, Carrascosa MJ, MartÃn-Caballero J, Flores JM, Diaz-Meco MT, Moscat J, Serrano M |
Journal | EMBO Rep |
Volume | 6 |
Issue | 6 |
Pagination | 577-83 |
Date Published | 2005 Jun |
ISSN | 1469-221X |
Keywords | Age Factors, Animals, Apoptosis, Butylhydroxybutylnitrosamine, Endometrial Neoplasms, Estradiol, Female, Histological Techniques, Immunoblotting, Male, Mice, Mice, Mutant Strains, Phenotype, Prostatic Neoplasms, Proteins, Receptors, Thrombin, Testosterone, Urinary Bladder Neoplasms, X-Linked Inhibitor of Apoptosis Protein |
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. |
DOI | 10.1038/sj.embor.7400421 |
Alternate Journal | EMBO Rep |
PubMed ID | 15877079 |
PubMed Central ID | PMC1369092 |
Related Faculty:
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.