Literature DB >> 12661038

Differential expression and/or activation of P38MAPK, erk1/2, and jnk during the initiation and progression of prostate cancer.

Aarti R Uzgare1, Paula J Kaplan, Norman M Greenberg.   

Abstract

BACKGROUND: Members of the mitogen-activated protein kinase (MAPK) family are capable of transducing signals from a wide variety of stimuli, including growth factors, G-protein coupled receptors, and cytokines that are likely to play a role in the initiation and/or progression of prostate cancer.
METHODS: The expression and activation of three members of the MAPK family, namely, erk, jnk, and p38MAPK was examined using Western blotting and immunohistochemistry during tumor progression in a transgenic mouse model for prostate cancer.
RESULTS: Activation of p38MAPK was significantly elevated (2.3-fold) in well-differentiated prostatic tumors compared to normal controls. Furthermore, prostatic intraepithelial neoplastic (PIN) lesions expressing activated p38MAPK were observed to be proliferative rather than apoptotic. Expression of activated erk1/2 also preferentially co-located to a sub-population of epithelial cells within PIN lesions that correlated with Ki67 expression. In dramatic contrast, activated forms of erk1/2, jnk, and p38MAPK were reduced or absent in late stage adenocarcinomas and metastatic deposits.
CONCLUSIONS: Erk1/2, jnk, and p38MAPKs are differentially expressed and/or activated during prostate cancer progression. Activation of both erk1/2 and p38MAPK occurs concomitant with prostatic epithelial cell proliferation and the initiation of prostate cancer while inactivation is contemporaneous with the emergence of the poorly differentiated metastatic and androgen-independent phenotype. Copyright 2003 Wiley-Liss, Inc.

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Year:  2003        PMID: 12661038     DOI: 10.1002/pros.10212

Source DB:  PubMed          Journal:  Prostate        ISSN: 0270-4137            Impact factor:   4.104


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