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- Title
Tumour-suppression activity of the proapoptotic regulator Par4.
- Authors
García-Cao, Isabel; Duran, Angeles; Collado, Manuel; Carrascosa, Maria J.; Martín-Caballero, Juan; Flores, Juana M.; Diaz-Meco, Maria T.; Moscat, Jorge; Serrano, Manuel
- 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 ζPKC (atypical protein kinase)-NF-κB (nuclear factor-κB)-XIAP pathway. These data show that Par4 has an important role in tumour suppression, with a particular relevance in the endometrium and prostate.
- Subjects
TUMOR suppressor proteins; PROSTATE cancer; HYPERPLASIA; CELLULAR pathology; PROTEINS; TUMORS; LABORATORY mice
- Publication
EMBO Reports, 2005, Vol 6, Issue 6, p577
- ISSN
1469-221X
- Publication type
Article
- DOI
10.1038/sj.embor.7400421