Abstract | BACKGROUND: Recent evidence has implicated the MAP kinase pathway with the development of androgen insensitive prostate cancer ( AIPC). We have previously reported gene amplification of critical members of this pathway with the development of androgen insensitive disease. METHODS:
Protein expression of Raf-1 was analyzed using immunohistochemistry (IHC) in a database of 65 paired tumor specimens obtained before and after the development of AIPC and correlated with other members of the pathway. RESULTS: Patients whose Raf-1 expression rose with development of AIPC had a significantly shorter median time to biochemical relapse compared to those whose expression fell or remained unchanged (1.16 vs. 2.62 years, P = 0.0005). In AIPC tumors, expression of Raf-1 correlated significantly with expression of HER2 and with expression of c-fos. CONCLUSIONS: We conclude that the HER2/Raf-1/AP-1 axis may promote the development of AIPC, leading to early relapse. Members of the pathway may act as novel therapeutic targets for patients.
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Authors | R Mukherjee, J M S Bartlett, N S Krishna, M A Underwood, J Edwards |
Journal | The Prostate
(Prostate)
Vol. 64
Issue 1
Pg. 101-7
(Jun 15 2005)
ISSN: 0270-4137 [Print] United States |
PMID | 15666389
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Androgens
- Proto-Oncogene Proteins c-raf
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Topics |
- Androgens
(metabolism)
- Disease Progression
- Humans
- Immunohistochemistry
- MAP Kinase Signaling System
(physiology)
- Male
- Prostatic Neoplasms
(metabolism, pathology)
- Proto-Oncogene Proteins c-raf
(metabolism)
- Recurrence
- Retrospective Studies
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