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Tumour‐suppression activity of the proapoptotic regulator Par4
Author(s) -
GarcíaCao Isabel,
Duran Angeles,
Collado Manuel,
Carrascosa Maria J,
MartínCaballero Juan,
Flores Juana M,
DiazMeco Maria T,
Moscat Jorge,
Serrano Manuel
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400421
Subject(s) - xiap , prostate , hyperplasia , endometrium , apoptosis , inhibitor of apoptosis , endocrinology , medicine , biology , cancer research , programmed cell death , caspase , biochemistry , cancer
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.