Raf-1 expression may influence progression to androgen insensitive prostate cancer.
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.
Mukherjee
R
R
Endocrine Cancer Group, Division of Cancer Studies and Molecular Pathology, University Department of Surgery, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Bartlett
J M S
JM
Krishna
N S
NS
Underwood
M A
MA
Edwards
J
J
D000728:Androgens / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies
D000728:Androgens; D019908:Proto-Oncogene Proteins c-raf