Differential expression and/or activation of P38MAPK, erk1/2, and jnk during the initiation and progression of prostate cancer.
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.
Uzgare
Aarti R
AR
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Kaplan
Paula J
PJ
Greenberg
Norman M
NM
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D018450:Disease Progression; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D014018:Tissue Distribution; D048051:p38 Mitogen-Activated Protein Kinases
D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases